Circadian-dependent retinal light damage in rats.
OBJECTIVE
To determine the relative susceptibility of rats to retinal light damage at different times of the day or night.


METHODS
Rats maintained in a dim cyclic light or dark environment were exposed to a single dose of intense green light beginning at various times. Normally, light exposures were for 8 or 3 hours, respectively, although longer and shorter periods were also used. Some animals were treated with the synthetic antioxidant dimethylthiourea (DMTU) before or after the onset of light. The extent of visual cell loss was estimated from measurements of rhodopsin and retinal DNA levels 2 weeks after light treatment. The time course of retinal DNA fragmentation, and the expression profiles of heme oxygenase-1 (HO-1) and interphotoreceptor retinol binding protein (IRBP) were determined 1 to 2 days after exposure.


RESULTS
When dark-adapted, cyclic light-reared or dark-reared rats were exposed to intense light during normal nighttime hours (2000-0800) the loss of rhodopsin or photoreceptor cell DNA was approximately twofold greater than that found in rats exposed to light during the day (0800-2000). The relative degree of light damage susceptibility persisted in cyclic light-reared rats after dark adaptation for up to 3 additional days. For rats reared in a reversed light cycle, the light-induced loss of rhodopsin was also reversed. Longer duration light treatments revealed that dim cyclic light-reared rats were three- to fourfold more susceptible to light damage at 0100 than at 1700 and that dark-reared animals were approximately twofold more susceptible. Intense light exposure at 0100 resulted in greater retinal DNA fragmentation and the earlier appearance of apoptotic DNA ladders than at 1700. The extent of retinal DNA damage also correlated with an induction of retinal HO-1 mRNA and with a reduction in IRBP transcription. Antioxidant treatment with DMTU was effective in preventing retinal light damage when given before but not after the onset of light.


CONCLUSIONS
These results confirm earlier work showing greater retinal light damage in rats exposed at night rather than during the day and extend those findings by demonstrating that a single, relatively short, intense light exposure causes a circadian-dependent, oxidatively induced loss of photoreceptor cells. The light-induced loss of photoreceptor cells is preceded by DNA fragmentation and by alterations in the normal transcriptional events in the retina and within the photoreceptors. The expression profile of an intrinsic retinal factor(s) at the onset of light exposure appears to be important in determining light damage susceptibility.
Organisciak
D T
DT
Petticrew Research Laboratory and the Departments of Biochemistry/Molecular Biology and Ophthalmology, Wright State University School of Medicine, Dayton, Ohio, USA. dto@wright.edu
Darrow
R M
RM
Barsalou
L
L
Kutty
R K
RK
Wiggert
B
B
D000818:Animals; D015152:Blotting, Northern; D002940:Circadian Rhythm / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects; D053938:DNA Fragmentation / Q000528:radiation effects; D003623:Dark Adaptation; D004587:Electrophoresis, Agar Gel; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D020869:Gene Expression Profiling; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1; D008027:Light / Q000009:adverse effects*; D008297:Male; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000209:etiology* / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D016166:Free Radical Scavengers; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D012177:Retinol-Binding Proteins; D012243:Rhodopsin; D013890:Thiourea; D000099214:Retinol-Binding Proteins, Interstitial; C038983:1,3-dimethylthiourea