Alleviation of constant-light-induced photoreceptor degeneration by adaptation of adult albino rat to bright cyclic light.
OBJECTIVE
To further test the hypothesis that light-adaptation-mediated photoreceptor protection works through inhibition of apoptosis by activation and/or upregulation of neuroprotective molecules.


METHODS
Albino rats were born and raised in 5-lux cyclic light (12 hours OFF and ON). At 8 weeks of age, animals were adapted to 400-lux cyclic light for different periods. Light damage was induced by exposure to constant light for 1 day at an illumination of 1700 lux. Animals were killed, and their eyes were removed for morphometric and biochemical analysis. TUNEL assay was used to evaluate photoreceptor cell apoptosis and Western blot analyses were used to determine the levels of basic fibroblast growth factor (bFGF), neuronal nitric oxide synthase (nNOS), and caspase-3.


RESULTS
Exposure of dim-reared rats to constant light for 1 day dramatically increased TUNEL-positive cells in the outer nuclear layer. Adaptation to 400-lux bright cyclic light for 4 days significantly reduced TUNEL-positive cells induced by exposure to constant light, which correlated with a significant increase in bFGF expression. Compared with control retinas, caspase-3 levels were not changed by exposure to constant light or after adaptation to 400 lux. There was a significant increase in nNOS level in the constant-light-exposed group, but not in the group adapted to 400-lux bright light before exposure to constant light.


CONCLUSIONS
The retina of the adult rat can rapidly upregulate neuroprotective mechanisms when switched from dim to bright cyclic light. Identification of the molecules involved in this process may allow rational development of therapeutic approaches to treat retinal degenerative diseases.
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Feng
F
Li
Wei
W
Cao
Robert E
RE
Anderson
D000221:Adaptation, Ocular / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D004596:Electroretinography; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008027:Light; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation
D016222:Fibroblast Growth Factor 2; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases