Photoreceptor cell damage by light in young Royal College of Surgeons rats

Purpose. To determine the effects of genetic background and light rearing c onditions on intense-light-mediated retinal degeneration in young RCS rats. Materials and methods. Albino rats, homozygous or heterozygous for the rdy gene were bred and born in dim cyclic light. At P7 they were moved to a dar k environment, and maintained there until exposure to intense visible (gree n) light at P18 or P25. Other rats remained in the dim cyclic light environ ment. At various times between P11 and P40 rats were killed for determinati ons of rhodopsin and photoreceptor cell DNA levels, western transblot analy sis of retinal S-antigen (arrestin) and a-transducin, or northern slot blot analysis of their respective mRNA levels. Results. At P18, unexposed dark maintained homozygous RCS rats and their ph enotypically normal heterozygous counterparts have nearly equivalent rhodop sin levels and photoreceptor cell DNA. Intense light exposure at this age, to 8 hours of continuous light or 3 hours of intermittent light, did not le ad to a loss of either rhodopsin or retinal DNA when compared with their re spective unexposed controls. At P25 rhodopsin levels were higher than at P1 8, while photoreceptor cell DNA was essentially the same as in the younger rats. However, intense light exposure at P25 resulted in substantial losses of rhodopsin and photorecptor cell DNA and the losses were greater in homo zygous rats than in heterozygous animals. Light damage of P25 fats maintain ed in dim cyclic light was essentially the same as in dark maintained homoz ygous rats, but no damage was found in the heterozygous animals. By western analysis, alpha-transducin levels in the retina increased with time in dar kness, while retinal S-antigen levels either remained the same or decreased during the period P15-P35. For rats in the cyclic light environment S-anti gen expression was greater than a-transducin at all ages. Slot blot analysi s of mRNAs for the two proteins generally followed the patterns seen by wes tern analysis. S-antigen mRNA was expressed at an earlier age and at higher levels than alpha-transducin in both types of rats from both light rearing conditions. Peak expression of S-antigen most often occurred at P18 in bot h the heterozygous and homozygous rats. Conclusions. The relative expressions of S-antigen and alpha-transducin in P18 and P25 rats correlates with their relative resistance to retinal light damage at P18 and their enhanced susceptibility at P25. Rats homozygous fo r the rdy gene also exhibit more damage than heterozygous animals when phot oreceptor cell DNA is used to estimate the extent of retinal light damage.