Phototoxic-induced photoreceptor degeneration causes retinal ganglion cell degeneration in pigmented rats

Abstract

Human retinitis pigmentosa results eventually in retinal ganglion cell (RGC) death, but how this occurs remains obscure. We have previously documented that in pigmented dystrophic Royal College of Surgeons (RCS) rats, photoreceptor degeneration is followed by retinal pigment epithelial (RPE) migration, formation of RPE-vascular complexes, and vascular displacement that causes RGC axonal compression and death. To investigate if phototoxic-induced photoreceptor degeneration is capable of causing similar pathologic events, we dilated the left pupil of pigmented nondystrophic RCS and Lister-Hooded rats and exposed them to light (3000 lux) for 72 hours. After various survival periods ranging between 0 hours and 21 months, the retinas were processed as whole mounts or in cross-sections. Two separate retinal degenerative events that may relate to differential light exposure across the retina were observed: an early arciform area of degeneration in the superotemporal retina and a delayed degeneration in the central and ventral retina. Although degeneration in the arciform area was always more severe and developed earlier (sensitive region), both of them showed quite comparable pathologic events to those described for dystrophic RCS rats. RGC axonal compression was seen as soon as 21 days after light exposure and RGC loss was seen 9 months after light exposure, mainly in the superotemporal retina, but also in the ventral retina. The results show that RGC loss in induced photoreceptor degeneration results from a similar series of events to those occurring as a consequence of inherited degeneration and therefore is not uniquely a property of inherited photoreceptor degeneration.