Differential effects of experimental glaucoma on intrinsically photosensitive retinal ganglion cells in mice.

ABSTRACT

Glaucoma is a group of eye diseases characterized by retinal ganglion cell (RGC) loss and optic nerve damage. Studies, including this study, support that RGCs degenerate and die in a type-specific manner following the disease insult. Here we specifically examined one RGC type, the intrinsically photosensitive retinal ganglion cell (ipRGC), and its associated functional deficits in a mouse model of experimental glaucoma. We induced chronic ocular hypertension (OHT) by laser photocoagulation and then characterized the survival of ipRGC subtypes. We found that ipRGCs suffer significant loss, similar to the general RGC population, but ipRGC subtypes are differentially affected following chronic OHT. M4 ipRGCs, which are involved in pattern vision, are susceptible to chronic OHT. Correspondingly, mice with chronic OHT experience reduced contrast sensitivity and visual acuity. By comparison, M1 ipRGCs, which project to the suprachiasmatic nuclei to regulate circadian rhythmicity, exhibit almost no cell loss following chronic OHT. Accordingly, we observed that circadian re-entrainment and circadian rhythmicity are largely not disrupted in OHT mice. Our study demonstrates the link between subtype-specific ipRGC survival and behavioral deficits in glaucomatous mice. These findings provide insight into glaucoma-induced visual behavioral deficits and their underlying mechanisms.