Cone-Rod Dependence in the Rat Retina: Variation with the Rate of Rod Damage

PURPOSE. To assess the effect of accelerated rod damage on the integrity of cones in the rat retina. METHODS. Rhodopsin-mutant P23H-3 and Sprague-Dawley (SD) rats were raised in scotopic ambient conditions (12 hours dark, 12 hours 5 lux) and then exposed to photopic conditions (12 hours dark, 12 hours 300 lux). Rods and cones were assessed for cell death, outer segment (OS) morphology, and electroretinogram (ERG) responses. RESULTS. Cones in the P23H-retina were affected rapidly by photopic exposure. Exposure for 2 days caused 50% reductions in LM- and S-cone OS length and cone ERG responses, associated with and preceded by reductions in rod OS length and ERG responses. Although 2 days' exposure increased the rate of rod death, outer nuclear layer thinning was minimal, and no evidence of cone death was detected. In the SD retina, the same photopic exposure had no measurable effects on death rates, OS length, or ERG responses in either rods or cones. Longer (7 days) photopic exposure reduced cone and rod OS length and ERG responses in SD, as well as P23H-3 retinas, but less severely than in the P23H-3 strain. CONCLUSIONS. Cones are damaged rapidly in the P23H-3 retina when rod damage is accelerated by raised ambient illumination. This close dependence of cone integrity on rod integrity contrasts with the life-long persistence of cone function in the scotopic reared P23H-3 rat. In humans suffering comparable photoreceptor dystrophies, the maintenance of steady, low ambient light may, by minimizing acute rod damage, optimize the function of surviving cones. (Invest Ophthalmol Vis Sci. 2009;50:3017-3023) DOI:10.1167/iovs.08-3004