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    <h1>Aging Eyes, Infant Eyes, and Excitable Tissues</h1>
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<p class="nav"><span class="nav-left">Listed under <a href="/ray-peat.html">Ray Peat</a>.</span><span class="nav-right"><a href="/theme.html">Theme</a></span></p>
<p>From the <a href="https://raypeat.com/articles/articles/aging-eyes.shtml" target="_blank">original article</a> in 2006. Author: <a href="https://raypeat.com/" target="_blank">Ray Peat</a>.</p>
  <em>
<p>The eyes 
and the lungs are sensitive tissues that are easily harmed by inappropriate 
environmental exposure. They are especially sensitive in infancy and 
old age.</p>
<p>For 60 
years there have been controversies about the cause of 
retinopathy of prematurity, which has blinded tens of thousands of people.</p>
<p>Degeneration 
of the retina is the main cause of blindness in old people. Retinal 
injury is caused by ordinary light, when the eyes are sensitized by 
melatonin, prolactin, and polyunsaturated fats. Bright light isn't 
harmful to the retina, even when it is continuous, if the retina isn't 
sensitized.</p>

<p>Melatonin 
and prolactin are induced by stress, and darkness is a stress because 
it impairs mitochondrial energy production. </p>
<p>The polyunsaturated 
fats which accumulate in the brain and retina damage mitochondria.</p>
<p>Iron, 
which accumulates prenatally, and then again with aging, reacts with 
unsaturated fats during stress to destroy cells.</p>
<p>The popular 
supplements melatonin, tryptophan, fish oils, St. John's 
wort, and the various omega -3 oils, all increase the risk of retinal 
light damage and macular degeneration. 
Serotonin uptake inhibiting antidepressants are suspected to be able 
to cause it.</p>
<p>Processes 
similar to those that damage the over-sensitized retina can occur in 
other cells, as a result of stress. The substances that sensitize the 
retina to light-damage, can also increase the incidence of new or 
metastatic cancers.</p>

<p>Iron supplements and the 
use of supplemental oxygen, especially with a vitamin E deficiency exacerbated 
by excessive unsaturated fats in the diet, are still commonly used exactly 
when they can do the most damage.</p>
  </em>
<p>One 
of the recognized achievements of biology has been the demonstration 
of life’s universality, in the sense that organisms of all sorts use 
the same fundamental genetic code, and that yeasts, lizards, apes, and 
people have remarkably similar cellular systems, as well as a great 
amount of genetic similarity.</p>

<p>There 
has been another, less well recognized, sort of convergence going on 
in physiology and pathophysiology. Hans Selye’s concept of stress, 
“the syndrome of being sick,” Otto Warburg’s argument that a “respiratory 
defect” was behind all kinds of cancer, and the idea of free radical 
damage as a common factor in disease and aging, helped to create a more 
general way of looking at the nature of disease that superceded medicine’s 
theories of disease pathogens and genetic mutations, which created thousands 
of “disease entities,” none of which had much to do with the individuality 
of the patient or his environment.</p>
<p>The 
understanding that plants and animals have much biochemistry in common 
has gradually changed the assumptions of the science establishment, 
which until recently insisted that only “ionizing radiation” could 
affect animals or other organisms that lacked chlorophyll--and insisted 
that ionizing rays acted only on the DNA. Visible light, the textbooks 
said, was not “chemically active,” and so couldn’t possibly affect 
animals’ cells. In animals, coloration was seen mainly as decoration 
and disguise, rather than as a functional part of their biochemistry. </p>
<p>(Chemically, 
the meaning of “a pigment” is that it’s a chemical which selectively 
absorbs radiation. <strong>Old observations such as 
Warburg’s, that visible light can restore the activity of the “respiratory 
pigments,” showed without doubt that visible light is 
biochemically active. </strong>By the 1960s, several studies had been published 
showing the inhibition of respiratory enzymes by blue light, and their 
activation by red light. The problem to be explained is why the science 
culture simply couldn’t accept crucial facts of that sort.)</p>
<p>The 
retina, of course, was allowed (in the views of mainline science) to 
respond to ordinary light, but the few people who studied the biological 
effects of seasonal or daily cycles of light have until recently stayed 
very close to the nerve pathways leading from the retina to the pineal 
gland, because those pathways could be described in terms of an evolutionarily 
specialized “third eye.” Even with a doctrine of a genetically specialized 
link between the retina and a little of the animal’s physiological 
chemistry, the great, slow-witted science establishment has done its 
best to avoid thoughts of any deep interaction between an organism and 
its environment, by insisting that the organism runs according to a 
genetically determined “clock” which is located in a few cells in 
a certain area of the brain, and that nervous impulses from the retina 
have only the small privilege of “setting the clock.”</p>
<p>It 
didn’t matter to the academic and medical worlds that a professor, 
Frank A. Brown, had long ago disproved the idea of an innate genetic 
“clock,” because philosophy is much stronger than evidence. Leibniz 
had said that everything in the world runs on its own inner clock, without 
needing to perceive its surroundings, and this idea that everything 
in the world is a “windowless monad” resonated through the world 
of science, because it justified the pompous authoritarian attitudes 
of the experts who knew that anything that wasn’t already in their 
heads couldn’t be considered knowledge. <strong>If an organism’s “essence 
is contained in its genes,” then it clearly doesn’t interact in 
any meaningful way with most of its environment.</strong> This is the sort 
of culture that imbued research on the biology of light cycles.</p>

<p>When 
I moved from Mexico, first to Montana and then to Oregon in 1966, I 
became very conscious of how light affects the hormones and the health. 
(For example, in Montana I experienced an interesting springtime shedding 
of body hair.) Many people who came to cloudy Eugene to study, and who 
often lived in cheap basement apartments, would develop chronic health 
problems within a few months. Women who had been healthy when they arrived 
would often develop premenstrual syndrome or arthritis or colitis during 
their first winter in Eugene. </p>
<p>The 
absence of bright light would create a progesterone deficiency, and 
would leave estrogen and prolactin unopposed. Beginning in 1966, I started 
calling the syndrome “winter sickness,” but over the next few years, 
because of the prominence of the premenstrual syndrome and fertility 
problems in these seasonally exacerbated disorders, I began calling 
it the pathology of estrogen dominance. In the endocrinology classes 
I taught at the National College of Naturopathic Medicine, I emphasized 
the importance of light, and suggested that medicine could be reorganized 
around these estrogen-related processes. If the sparrows of Times Square 
mated in the winter because of the bright lights, it seemed clear that 
bright artificial light would be helpful in regulating human hormones.</p>
<p>In 
our lab at the University of Oregon, our hamsters would try to hibernate, 
even though they were in temperature-controlled laboratories with regular 
cycles of artificial light. (The ceiling lights provided only dim illumination 
inside their cage boxes, so they were probably in a chronic state of 
light deprivation, which probably increased their sensitivity to the 
weak environmental cues that Frank Brown had investigated, possibly 
microwaves that easily penetrated the lab walls.) During the winter, 
when they were infertile, I found that their thymus glands practically 
disappeared. The mechanism seemed to include the increase of pineal 
gland activity (probably increasing melatonin synthesis) in the winter, 
under the intensified activity of the “sympathetic nervous system” 
(with increased activity of adrenalin and other catecholamines), and 
the melatonin was apparently a signal for suppressing fertility during 
the stressful winter. In some animals (Shvareva and Nevretdinova, 1989), 
estrogen is increased during hibernation, contributing to the reduction 
of body temperature.</p>
<p>In 
1994 A.V. Sirotkin found that melatonin inhibits progesterone production 
but stimulates estrogen production, and it’s widely recognized that 
melatonin generally inhibits the thyroid hormones, creating an environment 
in which fertilization, implantation, and development of the embryo 
are not possible. This combination of high estrogen with low progesterone 
and low thyroid decreases the resistance of the organism, predisposing 
it to seizures and excitotoxic damage, and causing the thymus gland 
to atrophy.</p>
<p>Cyclical 
exposure to melatonin can have an effect on the reproductive system 
opposite to that of chronic exposure, and the way exogenous melatonin 
is delivered to the animal can have unexpected effects on the actual 
amount of melatonin circulating in the blood (Wright and Alves, 2001). 
The actual amount of melatonin in the tissues, its relation to the normal 
cycling of the animal, and the influence of temperature, are often disregarded 
in melatonin research, making it hard to interpret many of the publications. </p>
<p>There 
is a lot of talk about melatonin’s function as an antioxidant, but, 
like so many other “antioxidants,” melatonin can act as a pro-oxidant 
at physiologically relevant concentrations<strong>;</strong> some studies have 
found that it, like estrogen, increases the activity of the pro-oxidative 
free radical nitric oxide (which acts like melatonin on pigment cells, 
causing them to lighten). The promoters of estrogen are also making 
claims that estrogen is a protective antioxidant, though that isn’t 
true of physiological concentrations of estrogen, which can catalyze 
intense oxidations. The market culture seems to guide most research 
in these substances.</p>

<p>Almost 
any kind of stress increases the formation of melatonin.</p>
<p>In 
some animals, melatonin 
has been shown to be responsible for whitening of the hair during the 
winter.  In some species it acts directly on the pigment cells, 
but in other species it seems to inhibit the action of the melanocyte 
stimulating hormone. </p>
<p>In 
snowy climates, it’s “ecologically” rational for animals to turn 
white in the winter, for camouflage. But tadpoles also turn white in 
the dark, or under the influence of melatonin, and the biological meaning 
of that isn’t so clear. It’s possible that being white would reduce 
their loss of heat through radiation, but I think it is more likely 
that it relates to an increased ability of weak radiation to penetrate 
their tissues, rather than being stopped near the surface by the melanin 
in the skin. The absence of melanin makes them more sensitive to light. 
Bright light suppresses their melatonin, and makes them turn dark brown 
or black, and this protects them from bright sunlight.</p>
<p>In 
the retina, melatonin increases the sensitivity of the cells to dim 
light. It, along with prolactin, another nocturnal hormone, helps to 
produce dark adaptation of the eyes.</p>
<p>Melatonin 
increases the concentration of free fatty acids during the night (John, 
et al., 1983; John and George, 1976)), so it’s interesting that one 
of the long-chain highly unsaturated fatty acids, DHA (docosahexaenoic 
acid), also increases the light sensitivity of the retina.</p>
<p>Melatonin 
lowers body temperature, causes vasoconstriction in the brain, heart, 
and other organs, and slows reactions. An antagonist to melatonin acts 
as an antidepressant, reducing “behavioral despair” resulting from 
stress. (Dubocovich, et al., 1990.) So, in the behavioral sense, melatonin 
reduces sensitivity, yet it increases the eyes’ sensitivity to light, 
causing them to be injured by light that would otherwise be harmless.</p>

<p>Since 
a hibernating animal under the influence of melatonin can become very 
cold, the light-sensitizing function of melatonin is probably related 
to the biological need to be roused out of the torpor occasionally. 
(Hibernators apparently have to warm up occasionally to sleep in the 
ordinary manner.) Melatonin is said to intensify dreaming, which is 
part of the process of arousal from sleep. </p>
<p>All 
of the stress-related hormones increase during the night. One of the 
ways these hormones of darkness act is to increase the sensitivity to 
light, in a process that is an important adaptation for organisms in 
dim light. In the night, our ability to see (and respond to) dim light 
is increased. But dark-adapted eyes are very sensitive to injury by 
bright light. Light that ordinarily wouldn’t harm the eyes, will do 
serious damage when the eyes are dark adapted.</p>
<p>In 
thinking about the effects of stress and oxygen deprivation, I read 
the studies demonstrating that the formation of the oxygen-wasting age 
pigment, lipofuscin, is increased by estrogen, by oxygen deprivation 
(in carp living below the ice, or even in fetuses), by metals such as 
iron, by x-rays, and by highly unsaturated fats.</p>
<p>Free 
fatty acids that are mobilized from storage tissues in the night and 
in the winter also tend to increase with aging, as the ability to tolerate 
stress decreases. Poor circulation and lipofuscin tend to be associated, 
in a vicious cycle. This means that the retina becomes easier to injure 
by light in old age, for some of the same reasons that the infant’s 
retina is susceptible.  </p>
<p>The 
fetus accumulates a very large amount of iron, and it absorbs melatonin 
from the maternal circulation. Prolactin is sometimes elevated in the 
newborn. Premature babies are often given extra oxygen, which tends 
to cause vasoconstriction by displacing carbon dioxide. Melatonin’s 
ability to cause vasoconstriction means that stress makes supplemental 
oxygen more toxic. Synthetic glucocorticoids are often given to premature 
babies, adding to the risk of retinal damage.</p>
<p>When 
the mother has been given iron supplements during pregnancy, along with 
unsaturated oils in the diet, the baby is likely to be born with a vitamin 
E deficiency and suppressed thyroid function, increasing the probability 
that it will be jaundiced, leading to treatment of the jaundice with 
exposure to very bright light.</p>

<p>Although 
Yandell Henderson had already, in 1928, explained the need for carbon 
dioxide to be used with oxygen for resuscitating infants or adults, 
medical researchers and hospital workers could never accept the idea, 
probably because of a fundamental misunderstanding of the Henderson-Hasselbalch 
equation. Animal experiments show that supplemental oxygen, without 
carbon dioxide, causes vasoconstriction, reducing the tissues’ supply 
of glucose as well as oxygen. In combination with too much light, especially 
blue light, it damages the retina. At hyperbaric pressure, oxygen causes 
seizures, as well as damage to the lungs and other tissues.</p>
<p>The 
contribution of bright light to retinal damage in babies has been denied 
in several recent publications, and these articles undoubtedly provide 
useful material for defense lawyers to use when hospitals are sued for 
causing blindness. One publication based on experiments with kittens 
concludes that bright light does not harm the newborn’s retina, but 
the comparison is between continuous light and intermittent light, rather 
than between bright light and dim light. Twelve hours of total darkness, 
rather than sparing the eye by reducing its exposure to light, would 
sensitize the eye. The only reason such appalling things can be published 
is that their conclusions protect the hospitals. </p>
<p>A 
few good studies of the effect of bright light on the retina, and the 
fact that dark-skinned people with more protective pigment in their 
eyes have a lower incidence of retinopathy of prematurity, make it clear 
that the ordinary laws of physics and chemistry actually do apply to 
the infant eye.  </p>
<p>Light 
and stress, especially with excess iron, damage the retina when the 
cells contain too much PUFA, since these fats react with light and free 
radicals. The nocturnal/stress hormones, especially prolactin and melatonin, 
make the retina more sensitive to light, and more easily damaged. (It's 
too much darkness that sets up the problem, since the eyes will adapt 
to excess light, but darkness increases their sensitivity.) </p>
<p>The 
use of lasers to operate on eyes produces intense inflammation of the 
eye, but even at low dose the diffusing light causes retinal/macular 
damage.</p>
<p>Cytochrome 
oxidase is one of the enzymes damaged by stress and by blue light, and 
activated or restored by red light, thyroid, and progesterone. It's 
a copper enzyme, so it's likely to be damaged by excess iron. It is 
most active when it is associated with a mitochondrial lipid, cardiolipin, 
that contains saturated palmitic acid<strong>;</strong> the substitution of polyunsaturated 
fats lowers its activity. Mitochonrial function in general is poisoned 
by the unsaturated fats, especially arachidonic acid and DHA.</p>

<p>Creating 
a “deficiency” of DHA, even when an oil of known toxicity is used 
to replace the omega -3 oils, prevents retinal damage from light. Despite 
evidence of this sort, Mead Johnson is going ahead with the marketing 
of its baby formula containing added DHA which is industrially extracted 
from algae. (Although the researchers who claim that DHA is beneficial 
haven’t answered my letters, a representative of the company that 
manufactures it did answer my question about the actual composition 
of the oil, and acknowledged that they don’t have any idea what the 
minor ingredients might be.)</p>
<p>When 
animals are made “deficient” in all the exogenous polyunsaturated 
fatty acids, linoleic and arachidonic acid as well as linolenic and 
DHA, they become remarkably resistant to all sorts of stress and toxins.</p>
<p>The 
polyunsaturated fats make the lungs more sensitive to excess oxygen 
or hyperventilation, they make the eyes more sensitive to light, and 
they make the brain more sensitive to fatigue.</p>
<p>The 
use of synthetic glucocorticoid hormone is standard in treating very 
premature babies, although it is known to contribute to eye damage. 
This is because it is considered necessary to improve the lung function 
of premature babies with respiratory distress. But there is no clear 
evidence that it is beneficial for lung function in the long run, and 
very clear evidence that it damages the brain and other organs. There 
is widespread agreement regarding the use of the glucocorticoids <strong><em>
prenatally</em></strong> to accelerate lung development in women who seem 
likely to deliver prematurely. Natural cortisol is a factor that promotes 
lung development prenatally. But cortisol is also a signal produced 
by a stressed fetus, that triggers the birth process. Cortisol, or the 
synthetic glucocorticoid, inhibits progesterone production, and stimulates 
estrogen production, activating uterine contractions and other processes 
that terminate the pregnancy.</p>
<p>Apparently, 
it doesn’t occur to many people that administering the glucocorticoid 
triggers premature birth, creating the problem they are intending to 
treat.</p>

<p>Recognizing 
causal connections between premature birth and respiratory distress 
and retinopathy of prematurity, it would be obvious that the greatest 
effort should be made to prevent the problems by improving the health 
of pregnant women. Hospitals, however, are invested in high technology 
systems for treating these problems, and even though their results are 
dismal, they can’t make money by getting pregnant women to eat enough 
protein to prevent preeclampsia, which is a major cause of premature 
birth, or by treating the problems with salt, magnesium, progesterone, 
thyroid, and aspirin when the women haven’t had a good diet.</p>
<p>Historically, 
preeclampsia has been blamed on the mother’s or fetus’s “bad genes,” 
and that cultural bias was the setting in which these high technology 
prenatal and neonatal systems developed. High technology “neonatology” 
derives from the same ideology that motivated Josef Mengele’s genetic 
research in Auschwitz. The idea of genetic determination is still motivating 
resistance to reasonable preventive approaches.</p>
<p>Thyroid, 
i.e., T3, is very effective in accelerating lung development in the 
fetus, and it doesn’t have any of the harmful effects of the synthetic 
glucocorticoids. It normalizes the hormones, increasing progesterone 
and decreasing estrogen, which are needed for full-term gestation, the 
opposite of the glucocorticoids’ effects. While the cortisol-like 
drugs damage the brain and other organs, thyroid and progesterone protect 
them.</p>
<p><strong>Old 
organisms, like newborns, are easily injured by all sorts of inappropriate 
excitation. As in premature babies, the aged eyes, lungs, and brain 
are especially sensitive to damage by stress.<em> But all organs are 
subject to the same kinds of damage. </em></strong>
Medical treatments for respiratory distress and macular degeneration 
in old people are often the same as those used so inappropriately for 
babies.<strong><em> The good health practices that can prevent the inflammatory 
and degenerative diseases can often make it possible for damaged tissues 
to recover, even in old age.</em></strong></p>

<p>The 
pituitary hormones, especially prolactin and TSH, are pro-inflammatory, 
and darkness increases TSH along with prolactin, 
so to compensate for a light deficiency, the pituitary should be well-suppressed 
by adequate thyroid. Armour thyroid or Thyrolar or Cynoplus, Cytomel, 
would probably be helpful. (Eye-drops containing T3 might be a way to 
restore metabolic activity more quickly.) Limiting water intake (or 
using salt generously) helps to inhibit prolactin secretion. The saturated 
fats protect against the body's stored PUFA, and keeping the blood sugar 
up keeps the stored fats from being mobilized. 
Aspirin (or indomethacin) is generally protective to the retina, analogously 
to its protection against sunburn. Adequate vitamin E is extremely important. 
There are several prescription drugs that protect against serotonin 
excess, but thyroid and gelatin (or glycine, as in magnesium glycinate) 
are protective against the serotonin and melatonin toxicities. Copper 
and magnesium deficiencies predispose to retinal damage. Red light is 
protective, blue light (or u.v.) is harmful, so wearing orange lenses 
would be helpful. Progesterone and pregnenolone, by reducing the stress 
reactions, should be helpful--in the eye diseases of infancy and old 
age, as they are in the respiratory distress syndromes.
</p>
<h2>References</h2>
<small>
<p>Eksp 
Klin Farmakol  1999 Mar-Apr; 62(2):58-60.<strong> 
[Melatonin lowers the threshold of light sensitivity of the human retina]</strong> 
; Arushanian EB, Ovanesov KB. Department of Pharmacology, Stavropol 
State Medical Academy, Russia. After chronic use of melatonin (3 mg 
before night-time for 14 days) campimetry 

showed a significant decrease of the threshold of brilliance sensitiveness 
of the retina in the absence of authentic changes of the sensorimotor 
response latency in individuals of the older age group. A connection 
between the eye light sensitivity and the direct effect of the hormone 
on the photoreceptors is suggested.</p>
<p>Cochrane 
Database Syst Rev 2001;4:CD001077. <strong>Restricted versus liberal oxygen 
exposure for preventing morbidity and mortality in 
preterm or low birth weight infants</strong> (Cochrane Review). Askie LM, 
Henderson-Smart DJ.</p>
<p>Prog 
Clin Biol Res  1989;312:95-112. <strong>The metabolism of omega-3 polyunsaturated 
fatty acids in the eye: the possible role of 
docosahexaenoic acid and docosanoids in retinal physiology and ocular 
pathology.</strong> Bazan NG.</p>
<p>Biull 
Eksp Biol Med  1976 Oct;82(10):1181-3. <strong>[Role of the biological 
activity of serotonin in the production of the &quot;shock lung&quot; 

syndrome.] ;</strong> Bazarevich GI, Deviataev AM, Likhtenshtein AO, Natsvlishvili 
BP, Sadeko MK.</p>
<p>Invest Ophthalmol Vis Sci  1993 Sep;34(10):2878-80. <strong>
An elevated hematogenous photosensitizer in the 
preterm neonate.</strong> Bynoe LA, Gottsch JD, Sadda SR, Panton RW, Haller 
EM, Gleason CA.</p>
<p>Eur 
J Endocrinol 1995 Dec;133(6):691-5. <strong>Melatonin enhances 
cortisol levels in aged but not young women.</strong> Cagnacci A, Soldani 
R, Yen SS</p>

<p>Am 
J Psychiatry  1976 Oct;133(10):1181-6. <strong>Negative effects of 
melatonin on depression.</strong> Carman JS, Post RM, Buswell R, Goodwin 
FK. In order to test the efficacy of the pineal neurohumor melatonin 
on depression, the hormone was administered in varying doses to six 
moderately to severely depressed patients and two patients with Huntington's 
chorea in double-blind crossover study. <strong>Melatonin exacerbated symptoms 
of dysphoria in these patients, as well as causing a loss of sleep and 
weight and a drop in oral temperature. 
Melatonin increased cerebrospinal fluid 
5-hydroxyindoleacetic acid and calcium</strong> in three of four patients 
studied. The authors discuss the implications of this finding.</p>
<p>Neuroendocrinol 
Lett  2001 Dec;22(6):432-4. <strong>Melatonin shortens the survival 
rate of Ehrlich ascites-inoculated mice.</strong> Catrina SB, Curca E, Catrina 
AI, Radu C, Coculescu M. Dept. Endocrinology II, University of Medicine 
and Pharmacy Carol Davila, Bucharest, Romania. <a href="mailto:sergiu-bogdan.catrina@molmed.ki.se" target="_blank">sergiu-bogdan.catrina@molmed.ki.se</a> 

“The average survival rate of the animals treated with melatonin was 
shorter (14.8+/-2.23 days) compared to control animals (21.9+/-2.21 
days)(p=0.01).” CONCLUSION: “In our model, melatonin had a deleterious 
effect on the survival rate raising the question whether it is correct 
to assume that the hormone shows lack of adverse reactions.”</p>
<p>J 
Neurochem  1988 Apr;50(4):1185-93. <strong>Induction of intracellular 
superoxide radical formation by arachidonic acid and by polyunsaturated 
fatty acids in primary astrocytic cultures.</strong> Chan 
PH, Chen SF, Yu AC.</p>
<p>Graefes 
Arch Clin Exp Ophthalmol 1993 Jul;231(7):416-23. <strong>Inhibition of 
cytochrome oxidase and blue-light damage in rat retina.</strong> Chen E. 
St. Erik's Eye Hospital, Karolinska Institute, Stockholm, Sweden.<strong> 
The activity of cytochrome oxidase, outer nuclear layer thickness, and 
edema were quantitatively evaluated in the blue-light exposed rat retina.</strong> 
Dark-adapted or cyclic-light reared rats were exposed to blue light 
with a retinal dose of 380 kJ/m2. Immediately, 1, 2, and 3 day(s) after 
exposure, the retinas of six rats from each adaptation group were examined. 
There was no difference between the dark-adapted and cyclic-light reared 
rats. Immediately after light exposure, cytochrome oxidase activity 
decreased. The activity in the inner segments remained low at day 1, 
while severe edema was observed in the inner and outer segments. The 
outer nuclear layer thickness decreased 1-3 days after exposure. The 
blue-light exposure inhibited cytochrome oxidase activity and caused 
retinal injury. Similarity of the injury process in the dark-adapted 
and cyclic-light reared retinas suggests that rhodopsin was not involved. 
The inhibition of cytochrome oxidase could be a cause of retinal damage.</p>

<p>Acta 
Ophthalmol Suppl 1993;(208):1-50. <strong>Inhibition of enzymes by short-wave 
optical radiation and its effect on the retina.</strong> Chen E. Eye Laboratory, 
St. Erik's Eye Hospital, Stockholm, Sweden. “Exposure to short-wave 
optical radiation is a potential hazard for vision. In the present study, 
blue-light damage is studied in rat retina.” <strong>“Blue light inhibited 
cytochrome </strong><strong>oxidase</strong> 
at a retinal dose of about 110 kJ/m2. This inhibition was reversible, 
and is probably related to the light regulation of retinal metabolism. 
At a retinal dose of about 380 kJ/m2, the inhibition of cytochrome oxidase 
was followed consecutively by a probable redistribution of chlorine 
and potassium in the inner and outer segments, damage to the mitochondria 
in the inner segments, edema in the inner and outer segments, and progressive 
degeneration of photoreceptor cells. Dark adaptation did not increase 
the blue-light retinal injury. <strong>These findings support the hypothesis 
that inhibition of cytochrome oxidase is one of the causes of blue-light 
retinal damage.</strong>” </p>
<p>Aust 
N Z J Ophthalmol  1997 May;25 Suppl 1:S73-5. <strong>Retinal control 
of scleral precursor synthesis.</strong> Devadas M, Morgan</p>

<p>Eur 
J Pharmacol  1990 Jul 3;182(2):313-25. <strong>Antidepressant-like activity 
of the melatonin receptor antagonist, 
luzindole (N-0774), in the mouse behavioral despair test.</strong> Dubocovich 
ML, Mogilnicka E, Areso PM.</p>
<p>J 
Pharmacol Exp Ther  1988 Sep;246(3):902-10. <strong>Luzindole (N-0774): 
a novel melatonin</strong><strong> 
receptor antagonist.</strong> Dubocovich ML.</p>
<p>Exp 
Eye Res  1985 Oct;41(4):497-507. <strong>The diurnal susceptibility 
of rat retinal photoreceptors to light-induced damage.</strong> Duncan TE, 
O'Steen WK. Exposure of albino rats to high intensity light results 
in rapid, graded loss of photoreceptors. The hormonal status and age 
of an animal at the time of exposure affect the severity of light-induced 
retinal damage. The adrenal axis and pituitary hormones (prolactin) 
have been demonstrated previously to affect the degree of cell death 
in the retina. Because circadian rhythms for adrenal and pituitary secretion 
have been demonstrated in the rat, a series of experiments was undertaken 
to determine if a diurnal pattern of retinal susceptibility to light 
damage exists which might be related to endogenous endocrine rhythms. 
Male Sprague-Dawley rats were exposed to 4 hr of high intensity fluorescent 
light for 8 consecutive days during different phases of the 14:10 hr 
light: dark animal room light cycle. Morphometric analysis performed 
at the light microscopic level 2 weeks after exposure demonstrated a 
differential susceptibility to light-induced cell death depending upon 
the period during the light-dark cycle when animals received their daily 
light exposure. Neuronal cell death was confined to the outer nuclear 
layer as previously described. <strong>The retinas of animals exposed during 
the middle of the dark period or during the first 5 hr of the light 
period were significantly more damaged than the retinas of animals exposed 
during the last 9 hr of the light period.</strong> Control groups for the 
relative amounts of dark-adaptation between groups suggested that the 
diurnal susceptibility to light damage was not solely dependent upon 
the degree of dark adaptation. These results demonstrate a diurnal susceptibility 
of photoreceptors to light-induced cell death.</p>

<p>Nature  
1983 Dec 22-1984 Jan 4;306(5945):782-4. <strong>Melatonin is a potent modulator 
of dopamine release in the retina.</strong> Dubocovich ML.</p>
<p>Semin 
Perinatol  2000 Aug;24(4):291-8. <strong>Environmental light and the 
preterm infant. </strong>Fielder AR, Moseley MJ. The lighting environment 
of the preterm baby is quite unlike that experienced at any other time 
of life. Physical and physiological factors control how much light reaches 
the retina of the preterm baby. With respect to the former, although 
many neonatal intensive care units are brightly and continuously lit, 
there is a trend to employ lower levels of illumination and to introduce 
cycling regimens. Physiological determinants of the retinal light dose 
include: eyelid opening and transmission, pupil diameter and the transmission 
characteristics of the ocular media. Early exposure to light does not 
significantly hasten or retard normal visual development, and it is 
not a factor in the development of retinopathy of prematurity. However, 
ambient neonatal intensive care unit illumination may be implicated 
in some of the more subtle visual pathway sequelae that cannot be attributed 
to other major complications of preterm birth including altered visual 
functions and arrested eye growth.</p>
<p>Pediatrics  
1992 Apr;89(4 Pt 1):648-53. <strong>
Light and retinopathy of prematurity: does retinal location offer a 
clue?</strong> Fielder AR, Robinson J, Shaw DE, Ng YK, Moseley MJ. Nursery 
illumination has been implicated in the pathogenesis of retinopathy 
of prematurity (ROP), although the results of recent studies are conflicting. 
The data base for this article is a prospective ROP study on 607 infants 
of birth weight less than or equal to 1700 g including 35 larger siblings 
from multiple births when 1 infant fulfilled the birth weight criteria. 
Retinopathy commences preferentially in the nasal retina of the most 
immature neonate and is less likely to develop, or its onset is delayed, 
in the superior and inferior<strong> regions. These findings cannot be fully 
accounted for by regional vascular and 
neuroanatomical variations. Radiometric and physiological evidence suggests 
that the very immature neonate, most at risk of developing severe 
ROP, receives the greatest retinal 
irradiance. Furthermore, ROP commences in the areas of the retina receiving 
the highest light dose, and its onset is either retarded or inhibited 
in the darker retinal regions. Further studies are required to</strong> determine 
whether early exposure to light is a factor in the development of ROP. 
If a causal relationship is proven, here at least is one modality that 
can easily and immediately be controlled.</p>

<p>N 
Engl J Med  1985 Aug 15;313(7):401-4. <strong>Effect of bright light 
in the hospital nursery on the incidence of 
retinopathy of prematurity.</strong> Glass P, Avery GB, Subramanian KN, Keys 
MP, Sostek AM, Friendly DS. The preterm infant is subjected to prolonged 
exposure to ambient nursery illumination at levels that have been found 
to produce retinal damage in animals. We prospectively investigated 
the effect of exposure to light in two intensive care nurseries by comparing 
the incidence of retinopathy of prematurity among 74 infants from the 
standard bright nursery environment (median light level, 60 foot-candles 
[ftc]) with the incidence among 154 infants of similar birth weight 
for whom the light levels were reduced (median, 25 ftc). <strong>There was 
a higher incidence of retinopathy of 
prematurity in the group of infants who had been exposed to the brighter 
nursery lights,</strong> particularly in those with birth weights below 1000 
g (86 percent vs. 54 per cent, P less than 0.01 by chi-square test). 
We conclude that the high level of ambient illumination commonly found 
in the hospital nursery may be one factor contributing to retinopathy 
of prematurity and that safety standards with regard to current lighting 
practices should be reassessed.</p>
<p>Doc 
Ophthalmol  1990 Mar;74(3):195-203. <strong>Light and the developing 
retina. </strong>Glass P. George Washington University School of Medicine 
&amp; Health Sciences, Washington, DC. <strong>“Retinopathy of 
prematurity (ROP) has increased in the United States in the past decade.</strong>”</p>

<p>Pediatr 
Res  1987 Oct;22(4):414-6. Calcemic responses to photic and pharmacologic 
manipulation of serum melatonin. Hakanson DO, Penny R, Bergstrom WH.</p>
<p>Pediatr 
Res  1990 Jun;27(6):571-3. <strong>Pineal and adrenal effects on calcium 
homeostasis in the rat.</strong> Hakanson DO, Bergstrom WH.</p>
<p>Science  
1981 Nov 13;214(4522):807-9. <strong>Phototherapy-induced 
hypocalcemia in newborn rats: prevention by 
melatonin.</strong> Hakanson DO, Bergstrom WH.</p>
<p>Doc 
Ophthalmol  1992;79(2):141-50. <strong>Diurnal variations in the 
electroretinographic c-wave and retinal 
melatonin content in rats with inherited retinal dystrophy.</strong> Hawlina 
M, Jenkins HG, Ikeda H.</p>

<p><strong>J.A.M.A. 
90:353 (Feb. 25) 1928. The Prevention and Treatment of Asphyxia in the 
New-Born, Henderson, Yandell.</strong></p>
<p>Neuroendocrinology  
2001 Feb;73(2):111-22. <strong>Estrogen modulates 
alpha(1)/beta-adrenoceptor- induced signaling and 
melatonin production in female rat 
pinealocytes.</strong> Hernandez-Diaz FJ, Sanchez JJ, 
Abreu P, Lopez-Coviella I, Tabares L, Prieto L, Alonso R.</p>
<p>J 
Neurosci Res  1989 Oct;24(2):247-50. <strong>Brain 
mitochondrial swelling induced by arachidonic acid and other long chain 
free fatty acids.</strong> Hillered L, Chan PH.</p>
<p>J 
Neurosci Res  1988;19(1):94-100. <strong>Effects of 
arachidonic acid on respiratory activities in isolated brain mitochondria.</strong> 

Hillered L, Chan PH.</p>
<p>J 
Neurosci Res  1988 Aug;20(4):451-6. <strong>Role of 
arachidonic acid and other free fatty acids in 
mitochondrial dysfunction in brain 
ischemia.</strong> Hillered L, Chan PH.</p>
<p>J Neurosci Res  1989 Oct;24(2):247-50. <strong>
Brain mitochondrial swelling induced by 
arachidonic acid and other long chain free fatty acids.</strong> Hillered 
L, Chan PH.</p>
<p>J 
Clin Epidemiol  1992 Nov;45(11):1265-87. <strong>Oxygen as a cause of 
blindness in premature infants: &quot;autopsy&quot; of a decade 
of errors in clinical epidemiologic research.</strong> Jacobson RM, Feinstein 
AR. Clinical Epidemiology Unit, Yale University School of Medicine, 
New Haven, CT 06510. “Several intellectual &quot;autopsies&quot; have 
recently reviewed errors in clinical epidemiologic studies of causation, 
such as the original claim that amyl nitrite &quot;poppers&quot; caused 
AIDS. The current autopsy was done to determine why it took<strong> more 
than a decade--1942 to 1954--to end an 
iatrogenic epidemic in which high-dose oxygen therapy led to 
retrolental fibroplasia (RLF) in premature infants, blinding about 10,000 
of them. </strong>The autopsy revealed a museum of diverse intellectual pathology.”</p>

<p>Curr 
Eye Res  2001 Jul;23(1):11-9. <strong>Rod outer segments mediate 
mitochondrial DNA damage and apoptosis in human retinal pigment epithelium. </strong>
Jin GF, Hurst JS, Godley BF.</p>
<p>Endocrinol 
Exp  1976 Jun;10(2):131-7.  <strong>Diurnal variation in the effect 
of melatonin on plasma and muscle free fatty acid levels in the pigeon.</strong> 
John TM, George JC. Pigeons maintained on standard diet and held under 
12 h daily photo-period in a controlled environmental room, were given 
intravenous injections of melatonin. A low dose (1.25 mg/kg body weight) 
of melatonin when given in the middle of the<strong> 
scotophase, produced a significant increase in plasma 
FFA when estimated at 20 min and 90 min post-injection, whereas no significant 
change was seen with injections given in the middle of the 
photophase. No significant change in muscle 
FFA level was obtained either during the 
photophase or the scotophase</strong> when estimated at 90 min postinjection. 
With a higher dose (5 mg/kg body weight) of melatonin given in the scotophase, 
on the other hand, a significant increase<strong> in both plasma as well 
as muscle FFA levels was obtained at 90 min</strong> post-injection but there 
was no effect on plasma FFA at 20 min or 90 min post-injection in the 
photophase and at 20 min in the scotophase. It is concluded that melatonin 
has a lipid mobilizing action in the pigeon when administered during 
the scotophase.</p>

<p>Arch 
Int Physiol Biochim  1983 Jul;91(2):115-20. <strong>Diurnal impact of 
locomotory activity and melatonin and 
N-acetylserotonin treatment on blood metabolite levels in the rainbow 
trout.</strong> John TM, Beamish FW, George JC. In rainbow trout forced to 
swim continuously at sustained speeds for six weeks, selected doses 
of melatonin or N-acetylserotonin (1.25 and 5.0 mg/kg body weight) injections 
caused no change in haematocrit. Melatonin did not produce any significant 
change in plasma glucose level either in the photophase or in the scotophase. 
However, diurnal variations were observed in the effect of melatonin 
on plasma free fatty acids (FFA). Melatonin was ineffective in causing<strong> 
any change in plasma FFA level during 
photophase but during scotophase, the higher dose (5.0 mg/kg) produced 
an increase in FFA while the lower dose (1.25 mg/kg) had no effect, 
N-acetylserotonin administration produced diurnal</strong> variation in its 
effect on both plasma glucose and FFA. The higher dose of N-acetylserotonin 
brought about a drop in plasma glucose level during photophase, but 
both doses were ineffective during scotophase. N-acetylserotonin produced 
no change in FFA during photophase, but during scotophase tended to 
lower FFA level. It is suggested that exercise shortens the time required 
to cause a hypoglycemic effect of N-acetylserotonin during photophase, 
blocks FFA release-inhibiting action of melatonin observed in photophase, 
and minimizes the time required for the FFA mobilizing action of melatonin 
in scotophase.</p>
<p>J 
Neural Transm  1977;40(2):87-97. <strong>The adrenal medulla may mediate 
the increase in pineal melatonin synthesis induced by stress, but not 
that caused by exposure to darkness.</strong> Lynch HJ, Ho M, Wurtman RJ.</p>
<p>Bull 
Acad Natl Med  2000;184(2):415-28; discussion 428-30. <strong>[Pulmonary 
toxicity of oxygen]</strong> [Article in French] Mantz JM, Stoeckel ME.</p>

<p>Br 
J Pharmacol  1977 Dec;61(4):607-14. <strong>The action of 
melatonin on single amphibian pigment cells in tissue culture.</strong> Messenger 
EA, Warner AE.</p>
<p>Oftalmol 
Zh  1989;(8):469-73. <strong>[The 
early diagnosis, evaluation of treatment results and 
modelling of certain aspects of the pathogenesis of retinal dystrophy]</strong> 
; Mironova EM, Pavlova ON, Ronkina TI. The paper analyses results after 
a study of the functional state of pigmented epithelium and the retina 
in patients with a dry form of senile macular dystrophy as well as of 
experimental simulation of retinal dystrophy with the help of melatonin 
and its treatment by taurine. <strong>Melatonin in 10(-3) M concentration 
leads to development of dystrophic changes</strong> in pigmented epithelium 
and interacting with it structures, this being testified by remarkable 
lowering of EOG parameters and electron microscopic findings. Taurine 
in 10(-3) <strong>M concentration blocks the action of 
exogenic melatonin as well as has a pronounced positive action on metabolism 
of dystrophic changes in the pigmented epithelium and photoreceptors. 
Examination of patients with different stages of a dry form of senile</strong> 
macular dystrophy revealed statistically significant reduction of KA 
cEOG at the initial stage of the disease in the presence of normal ERG 
parameters. In 18% of patients, supernormal values of KA were recorded, 
that are likely to reflect the presence of &quot;predystrophic hyperactivity&quot; 

of the pigmented epithelium cells. In progression of the process, the 
further reduction of electrophysiologic values was recorded. The data 
obtained speaks about the important role of pigmented epithelium pathology 
in the pathogenesis of senile macular dystrophy and about high information 
value of the cEOG method for detection of early stages of the disease. 
It is believed that disturbances in melatonin metabolism can be one 
of causes leading to development of retinal dystrophy.</p>
<p>J 
Clin Endocrinol Metab  1977 Oct;45(4):768-74. <strong>The effects of 
oral melatonin on skin color and on the release of pituitary hormones.</strong> 
Nordlund JJ, Lerner AB. “We studied the effects of prolonged ingestion 
of melatonin, 1 g per day, on skin color and the serum levels of pituitary 
hormones in 5 human subjects with hyperpigmented skin. Melatonin 
lightened hyperpigmented skin of one patient with untreated adrenogenital 
syndrome, but had no effect on three patients' skin with idiopathic 
hyperpigmentation and one patient with treated Addison's disease.”</p>
<p>Invest 
Ophthalmol  1976 Oct;15(10):869-72. <strong>Hormonal influences on photoreceptor 
damage: the pituitary gland and ovaries.</strong> Olafson RP, O'Steen WK. 
To determine whether the absence of pituitary or ovarian hormones would 
influence retinal degeneration, female albino rats were either hypophysectomized 
(HYPEX) or ovariectomized (OVEX) before pubery. Later, they were exposed 
to continuous light for periods up to 45 days. Retinas evaluated by 
light microscopic measurements showed damage to the outer nuclear layer 
(ONL) and photoreceptor layer in both the operated and intact, control 
rats. However, the degree of damage observed in retinas of HYPEX and 
OVEX rats was significantly less than that observed in retinas of intact 
rats exposed to the same lighting conditions. Therefore, hypophysectomy 
and ovariectomy, which influence the normal development of sexual maturation 
when performed on immature rats, significantly reduce photoreceptor 
damage in adult rats exposed to continuous light.</p>
<p>Invest 
Ophthalmol Vis Sci  1996 Oct;37(11):2243-57. <strong>Retinal light damage 
in rats with altered levels of rod outer segment 
docosahexaenoate. Organisciak DT, Darrow 
RM, Jiang YL, Blanks JC.</strong> 

PURPOSE: To compare retinal light damage in rats with either normal 
or reduced levels of rod outer segment (ROS) docosahexaenoic acid. METHODS: 
Weanling male albino rats were maintained in a weak cyclic light environment 
and fed either a nonpurified control diet or a purified diet deficient 
in the linolenic acid precursor of docosahexaenoic acid (DHA). Half 
the rats on the deficient diet were given linseed oil, containing more 
than 50 mol% linolenic acid, once a week to maintain ROS DHA at near 
normal levels. Diets and linseed oil supplementation were continued 
for 7 to 12 weeks. To replenish DHA in their ROS, some 10-week-old rats 
on the deficient diet were given linseed oil three times a week for 
up to 3 additional weeks. Groups of animals were killed at various times 
for ROS fatty acid determinations or were exposed to intense green light 
using intermittent or hyperthermic light treatments. The extent of retinal 
light damage was determined biochemically by rhodopsin or photoreceptor 
cell DNA measurements 2 weeks after exposure and morphologically by 
light and electron microscopy at various times after light treatment. 
RESULTS: <strong>Rats maintained for 7 to 12 weeks on the 
linolenic acid-deficient diet had significantly lower levels of 
DHA</strong> and significantly higher levels of n-6 docosapentaenoic acid 
(22:5n-6) in their ROS than deficient-diet animals supplemented once 
a week with linseed oil or those fed the nonpurified control diet. As 
determined by rhodopsin levels and photoreceptor cell DNA measurements, 
deficient diet rats<strong> exhibited protection against retinal damage from 
either intermittent or hyperthermic light exposure. However, the unsaturated 
fatty acid content of ROS</strong> from all three dietary groups was the 
same and greater than 60 mol%. In 10 week-old deficient-diet rats given 
linseed oil three times a week, ROS DHA was unchanged for the first 
10 days, whereas 22:5n-6 levels declined by 50%. After 3 weeks of treatment 
with linseed oil, ROS DHA and 22:5n-6 were nearly the same as in rats 
supplemented with linseed oil from weaning. The time course of susceptibility 
to retinal light damage, however, was different. Hyperthermic light 
damage in rats given linseed oil for only 2 days was the same as for 
rats always fed the deficient diet. Six days after the start of linseed 
oil treatment, retinal light damage was the same as in rats given the 
linseed oil supplement from weaning. Morphologic alterations in ROS 
of linseed oil-supplemented rats immediately after intermittent light 
exposure were more extensive than in either the deficient-diet animals 
or those fed the control diet. The deficient-diet rats also exhibited 
better preservation of photoreceptor cell nuclei and structure 2 weeks 
after exposure. CONCLUSIONS: Rats fed a diet deficient in the linolenic 
acid precursor of DHA are protected against experimental retinal light 
damage. The relationship between retinal light damage and ROS lipids 
does not depend on the total unsaturated fatty acid content of ROS; 
the damage appears to be related to the relative levels of DHA and 22:5n-6.</p>
<p>Exp 
Neurol  1970 May;27(2):194-205.<strong> Retinal and optic nerve 
serotonin and retinal degeneration as influenced by 
photoperiod.</strong> O'Steen WK.</p>
<p>Invest 
Ophthalmol Vis Sci  1982 Jan;22(1):1-7. <strong>Antagonistic effects 
of adrenalectomy and ether/surgical stress on light-induced photoreceptor 
damage.</strong> O'Steen WK, Donnelly JE. Light-induced damage to retinal 
photoreceptors in influenced by the endocrine status of the animal during 
the period of exposure. Experimental manipulation of the pituitary gland 
and of prolactin levels has been shown to affect retinal damage in rats 
exposed to visible light. When rats are experimentally stressed, prolactin 
secretion from the pituitary gland occurs as does secretion of adrenocorticotropic 
hormone (ACTH), which stimulates the release of adrenal cortical hormones. 
Since prolactin appears to influence retinal damage and since stressed 
animals have increased serum levels of prolactin, a comparison of photoreceptor 
damage in animals in which the adrenal glands were removed or which 
had been experimentally stressed was undertaken in this study. Adrenalectomized 
rats had thicker outer nuclear layer (ONL) measurements than those found 
in sham-operated animals. Stressed rats had severely damaged retinas 
with cystic degeneration and significantly reduced ONL thickness measurements 
as compared to retinas of unstressed and adrenalectomized rats. <strong>Therefore 
hormones of the pituitary-adrenal system appear to be involved in the 
damage to the retina by light, and this response may be related to an 
interaction or synergism between the adrenal gland, stress, and 
prolactin secretion.</strong></p>

<p>Brain 
Res  1990 Nov 26;534(1-2):99-105. <strong>Water deprivation protects 
photoreceptors against light damage.</strong> O'Steen WK, Bare DJ, Tytell 
M, Morris M, Gower DJ. “Photoreceptor cell death after light-damage 
and during aging in rats is associated with the hormonal status of the 
animal, as well as other environmental and intrinsic factors. Restricted 
caloric intake extends the life of rodents and is usually accompanied 
by a reduction in water consumption. In this study, male and female 
rats were placed on restricted water intake for either 3 or 7 days to 
induce dehydration.” “Photoreceptor cells of 7-day, dehydrated male 
and female rats survived light-damage significantly better than those 
allowed water ad libitum; however, after 3 days of water restriction, 
only the male rats demonstrated protection from photodamage.” “AVP 
increased by 350% during the 7-day period of dehydration. Protection 
of photoreceptors from light-damage in this study may be correlated 
with osmotically stimulated changes in the retinas of dehydrated animals.”</p>
<p>Brain 
Res  1985 Oct 7;344(2):231-9. <strong>Neuronal damage in the rat retina 
after chronic stress.</strong> O'Steen WK, Brodish A. Long-term exposure 
to escapable foot shock has been used to determine if chronic stress 
influences neuronal cell death in the retina of albino and pigmented 
rats. Histopathologic and morphometric approaches analyzed changes in 
photoreceptors and neurons of the bipolar and ganglion cell layers of 
the retina. Albino Fischer rats when exposed to chronic stress for 4-8 
h daily for 1 week to 6 months, developed severe retinal damage, as 
compared to unstressed control retinas, with reduction in photoreceptor 
and bipolar neurons, particularly in the superior central retina. The 
damage was observed in male and female rats, but males appeared to be 
more susceptible to the influence of stress than female animals. Ganglion 
cells were unaffected. Photoreceptor destruction did not occur in Long-Evans 
pigmented rats under identical experimental conditions. The results 
suggest that: <strong>input of the sensory stimulus, light, to the retina 
of stressed rats augmented neuronal damage and might be required for 
its initiation;</strong> and hormones and/or neurotransmitters associated 
with long-term chronic stress might be related to increased neuronal 
cell death in the mammalian retina.</p>
<p>Invest 
Ophthalmol Vis Sci  1977 Oct;16(10):940-6. <strong>Effects of 
hypophysectomy, pituitary gland homogenates and transplants, and 
prolactin on photoreceptor destruction.</strong> O'Steen WK, Kraeer SL. “Prepubertal 
removal of the pituitary gland, which in young animals influences sexual 
maturation, reduces significantly the amount of retinal photoreceptor 
destruction when the rats are exposed to continuous illumination in 
adulthood. When crude pituitary gland homogenate is administered to 
adult rats hypophysectomized prior to puberty, photoreceptor destruction 
is more severe. Transplantation of whole pituitary glands to the kidney 
capsule of hypophysectomized 

rats also reduces the effect of pituitary gland removal and results 
in more extensive damage to receptor cells than found in hypophysectomized, 
adult animals. <strong>Hypophysectomized rats treated with 
prolactin had more severe retinal damage than untreated, 
hypophysectomized rats.”</strong> “Results of these studies indicate 
the hormones of the pituitary 
gland have a regulatory influence on the severity of light-induced, 
retinal photoreceptor damage in the rat.” </p>
<p>Life 
Sci  1985 Nov 4;37(18):1743-6. <strong>Stress-induced synthesis of 
melatonin: possible involvement of the endogenous 
monoamine oxidase inhibitor (tribulin).</strong> Oxenkrug GF, McIntyre IM.</p>
<p>Mech 
Ageing Dev  2000 Jan 10;112(3):169-83. <strong>Double bond content of 
phospholipids and lipid peroxidation negatively correlate with maximum 
longevity in the heart of mammals.</strong> Pamplona R, Portero-Otin M, Ruiz 
C, Gredilla R, Herrero A, Barja G.</p>

<p>Prostaglandins 
Leukot Essent Fatty Acids  
2001 Feb;64(2):75-80. <strong>Comparative studies on lipid 
peroxidation of microsomes and mitochondria obtained from different 
rat tissues: effect of retinyl palmitate.</strong> Piergiacomi VA, Palacios 
A, Catala A.</p>
<p>Curr 
Eye Res  1992 Oct;11(10):939-53. <strong>Oxygen-induced 
retinopathy in the rat: hemorrhages and 
dysplasias may lead to retinal detachment.</strong> Penn JS, Tolman BL, Lowery 
LA, Koutz CA.</p>
<p>Vision 
Res  1995 May;35(9):1247-64. <strong>Studies on the role of the retinal 
dopamine/melatonin system in experimental refractive errors in chickens.</strong> 

Schaeffel F, Bartmann M, Hagel G, Zrenner E.</p>
<p>Exp 
Clin Endocrinol Diabetes  1997;105(2): 109-12. <strong>Melatonin</strong><strong> and 
serotonin regulate the release of insulin-like growth factor-I, 
oxytocin and progesterone by cultured human 
granulosa cells.</strong> Schaeffer HJ, Sirotkin AV.</p>
<p>Zh 
Evol Biokhim Fiziol  1989 Jan-Feb;25(1):52-9. <strong>[Seasonal characteristics 
of the functioning of the hypophysis-gonad system in the 
suslik</strong> Citellus parryi] Shvareva NV, Nevretdinova ZG. “In females, 
FSH was found in the blood in October, being absent from November to<strong> 
January; beginning from February, it may be found both in sleeping and 
active</strong> animals.” <strong>“Estradiol secretion was noted in hibernating 
females, whereas progesterone was found in the blood only in May.”</strong></p>

<p>J 
Pineal Res  1985;2(1):39-49. <strong>Melatonin and 
N-acetylserotonin stress responses: effects of type of stimulation and 
housing conditions.</strong> Seggie J, Campbell L, Brown GM, Grota LJ.</p>
<p>Acta 
Ophthalmol Scand  
2001 Aug;79(4):428-30. <strong>Presumed 
sertraline maculopathy.</strong> Sener EC, Kiratli H.</p>
<p>Paediatr 
Perinat Epidemiol  1999 Apr;13(2):128-30. <strong>Effects of premature 
exposure to light: a credibility struggle.</strong> Silverman WA.</p>

<p>J 
Pineal Res  1994 Oct;17(3):112-7. <strong>Direct influence of 
melatonin on steroid, nonapeptide hormones, and cyclic nucleotide secretion 
by granulosa cells isolated from porcine ovaries.</strong> Sirotkin AV. <strong>
“It was found that melatonin is able to inhibit progesterone and stimulate 
estradiol secretion.”</strong> “The present observations suggest a direct 
effect of melatonin on the steroid, nonapeptide hormone, and cyclic 
nucleotide release from porcine ovarian cells.”</p>
<p>J 
Pineal Res  1994 Oct;17(3):112-7. <strong>Direct influence of 
melatonin on steroid, nonapeptide hormones, and cyclic nucleotide secretion 
by granulosa cells isolated from porcine ovaries.</strong> Sirotkin 
AV.</p>
<p>Prog 
Clin Biol Res  1989;312:229-49. <strong>Inhibitors of the 
arachidonic acid cascade in the management of ocular inflammation.</strong> 

Srinivasan BD, Kulkarni PS.</p>
<p>J 
Nutr  2000 Dec;130(12):3028-33. <strong>Polyunsaturated (n-3) fatty 
acids susceptible to peroxidation are increased in plasma and tissue 
lipids of rats fed docosahexaenoic acid-containing oils.</strong> Song JH, 
Fujimoto K, Miyazawa T.<strong> “Thus, high incorporation of (n-3) fatty 
acids (mainly DHA) into plasma and tissue lipids due to 
DHA-containing oil ingestion may undesirably affect tissues by enhancing</strong> 
susceptibility of membranes to lipid peroxidation and by disrupting 
the antioxidant system.”  </p>
<p>Acta 
Ophthalmol (Copenh) 1992 Feb;70(1):115-22. <strong>Effects of steady electric 
fields on human retinal pigment epithelial cell orientation and migration 
in culture.</strong> Sulik GL, Soong HK, Chang PC, Parkinson WC, Elner SG, Elner VM</p>

<p>Ned 
Tijdschr Geneeskd  2001 Dec 29;145(52):2521-5. <strong>[Administration 
of glucocorticosteroids to premature infants: increasing evidence of 
adverse effects]</strong> [Article in Dutch] van Bel F. <strong>“Neonatal 
glucocorticosteroid therapy is increasingly being used for the prevention 
of chronic lung disease in very premature infants. In the short term 
this therapy is usually successful. There is, however, increasing evidence 
for long-term adverse effects. In particular there seems to be an increased 
chance of abnormal brain development, which later results in 
locomotory dysfunction, developmental delay and cerebral palsy.</strong>”</p>
<p>Brain 
Res  1984 Feb 27;294(1):166-8. <strong>Pineal 
methoxyindoles depress calcium uptake by rat brain 
synaptosomes.</strong> Vacas MI, Keller Sarmiento MI, Cardinali DP.</p>
<p>Ann 
N Y Acad Sci  1994 Nov 17;738:408-18. <strong>Serotonin binding proteins: 
an in vitro model system for monoamine-related 
neurotoxicity.</strong> Vauquelin G, Del Rio MJ, Pardo CV. </p>

<p>J 
Hypertens Suppl  1985 Dec;3 Suppl 3:S107-9. <strong>Seasonal variation 
in the development of stress-induced systolic hypertension in the rat.</strong> 
Weinstock M, Blotnick S, Segal M. “Seasonal variation in blood pressure 
in human hypertensives prompted us to investigate whether such a phenomenon 
also occurs in rats made hypertensive by environmental stress.” <strong>
“Systolic pressure increased by 14-25 
mmHg after 6-8 weeks of stress from October to January. Artificial environmental 
light for 15 h prevented development of hypertension by stress, </strong>
which could also be reversed by acute administration of propranolol.” 
“Hypertensive rats had significantly greater relative heart and adrenal 
weights. This phenomenon can be explained by amplification of<strong> sympathetic 
pressor activity by stress hormones, adrenaline, 
corticosterone and prolactin, under the influence of 
melatonin.”</strong></p>
<p>Invest 
Ophthalmol Vis Sci  1992 May;33(6):1894-902. <strong>Melatonin increases 
photoreceptor susceptibility to light-induced damage.</strong> Wiechmann 
AF, O'Steen WK. <strong>“Pinealectomy has been shown to protect photoreceptors 
from light-induced damage, and melatonin treatment has been reported 
to increase the degree of photoreceptor damage in albino rats.</strong>” 
“The animals that received daily melatonin injections (100 micrograms) 
in the late afternoon (3 hr before lights off) for 1-3 days before photodamage 
showed an approximate 30% greater reduction compared with sham control 
animals in ONL thickness 
in the superior quadrant, the area most susceptible to light damage. 
Melatonin injections given after the photodamage did not affect ONL 
thickness. Although retinal susceptibility to light damage varied with 
time of day, the degree to which melatonin increased the degree of damage 
appeared unaffected by the time of day. These results suggest that melatonin 
may be involved in some aspects of photoreceptor sensitivity to light 
damage.”</p>

<p>J 
Neurochem  1986 Oct;47(4):1181-9. <strong>Effects of 
arachidonic acid on glutamate and gamma-aminobutyric acid uptake in 
primary cultures of rat cerebral cortical 
astrocytes and neurons.</strong> Yu AC, Chan PH, Fishman RA. </p>
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