The
melanopsin positive, intrinsically photosensitive retinal ganglion cells (ipRGCs) of the inner retina have been shown to send wide-ranging projections throughout the brain. To investigate the response of this important cell type during
retinal dystrophy, we use the Royal College of Surgeons (RCS) dystrophic rat, a major model of
retinal degeneration. We find that ipRGCs exhibit a distinctive molecular profile that remains unaltered during early stages of outer
retinal pathology (15 weeks of age). In particular, these cells express betaIII
tubulin, alpha-acetylated
tubulin, and
microtubule-associated proteins (MAPs), while remaining negative for other RGC markers such as neurofilaments,
calretinin, and
parvalbumin. By 14 months of age,
melanopsin positive fibers invade ectopic locations in the dystrophic retina and ipRGC axons/dendrites become distorted (a process that may involve
vascular remodeling). The morphological abnormalities in
melanopsin processes are associated with elevated immunoreactivity for
MAP1b and a reduction in alpha-acetylated
tubulin. Quantification of ipRGCs in whole mounts reveals reduced
melanopsin cell number with increasing age. Focusing on the
retinal periphery, we find a significant decline in
melanopsin cell density contrasted by a stability of
melanopsin positive processes. In addition to these findings, we describe for the first time, a distinct plexus of
melanopsin processes in the far peripheral retina, a structure that is coincident with a
short wavelength opsin cone-enriched rim. We conclude that some ipRGCs are lost in RCS dystrophic rats as the disease progresses and that this loss may involve
vascular remodeling. However, a significant number of
melanopsin positive cells survive into advanced stages of
retinal degeneration and show indications of remodeling in response to pathology. Our findings underline the importance of early intervention in human
retinal disease in order to preserve integrity of the inner
retinal photoreceptive network.