Light history and age-related changes in retinal light damage.
OBJECTIVE
To determine the effects of age and long-term light- or dark-rearing environments on acute, intense-light-mediated retinal degeneration.


METHODS
Male albino rats were maintained in a dim cyclic light environment or in darkness for as long as 1 year. When aged 2, 4, 8, and 12 months, some rats were given the synthetic antioxidant dimethylthiourea (DMTU) by intraperitoneal injection and were exposed to intense visible light for as long as 24 hours. Uninjected control rats were exposed to light at the same time. Other rats were treated with light of lower intensity for various periods. Two weeks after intense-light treatment, photoreceptor cell degeneration was estimated by determining the level of rhodopsin and by measuring the content of photoreceptor cell DNA. Light-induced changes in retinal DNA were analyzed immediately after exposure by neutral gel electrophoresis and by 8-hydroxy-deoxyguanosine measurements. Expression of the antioxidative stress protein heme oxygenase-1 (HO-1) was determined by northern blot analysis of mRNA in retinal extracts.


RESULTS
At all ages, rats reared in cyclic dim-light conditions had lower rhodopsin levels than did rats reared in darkness; photoreceptor cell DNA levels were unaffected by the rearing environment. Senescent losses in rhodopsin and retinal DNA were significant after rats were 12 months old. Dim-light-reared rats exhibited an age-related increase in retinal light damage susceptibility, whereas dark-reared rats were equally susceptible to damage at all ages. In both types of rats, the mechanism of light-induced cell death involved an apoptotic process, visualized by the pattern of DNA fragments on electrophoretic gels. The process also induced the expression of HO-1 mRNA. Photoreceptor cell loss determined by biochemical measurement, DNA fragmentation, and HO-1 induction were dramatically reduced by the administration of DMTU.


CONCLUSIONS
The age-related increase in susceptibility to retinal light damage in rats is influenced by their long-term daily light history. Decreasing retinal irradiance by dark-rearing eliminates the age-related increase in light damage, suggesting a correlation between light environment and retinal gene expression associated with damage. In all rats, retinal light damage resulted in a pattern of DNA fragmentation consistent with apoptotic cell death and in an increased expression of HO-1 mRNA. Antioxidant treatment greatly reduced apoptosis and HO-1 expression. This indicates that light damage involves an oxidative process that may also trigger apoptosis in the retina. The rat aging model may provide useful insights into the role of light environment associated with retinal degeneration in an aging human population.
Organisciak
D T
DT
Department of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio 45435, USA.
Darrow
R M
RM
Barsalou
L
L
Darrow
R A
RA
Kutty
R K
RK
Kutty
G
G
Wiggert
B
B
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000502:physiology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D003623:Dark Adaptation; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016166:Free Radical Scavengers / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1; D008027:Light / Q000009:adverse effects*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D012243:Rhodopsin / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D016166:Free Radical Scavengers; D012333:RNA, Messenger; D000080242:8-Hydroxy-2'-Deoxyguanosine; C038983:1,3-dimethylthiourea; D012243:Rhodopsin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D003849:Deoxyguanosine; D013890:Thiourea