Eye Disease And The Regulation Of Behavioral State By Light: Age Of Retinal Degeneration Determines Phenotype

Abstract

Purpose: : Specialized melanopsin ganglion cell circuits in the retina encode irradiance to regulate physiology and behavioral state. Despite the importance of this function of the eye, how eye disease affects 'irradiance responses' remains virtually unexplored. The purpose of this study was to determine how rod-cone photoreceptor degeneration affects responses to light, distinguishing between phenotypes attributable to loss of rod-cone input, and phenotypes arising from interaction of degeneration with development of these retinal circuits.

Methods: : A comparison of behavioral and pupillary responses to light was made in rd1 and rd10 mice, both having mutations in Pde6b that result in rod-cone degeneration, but with degeneration being later in rd10.

Results: : Retinal degeneration severely reduced irradiance sensitivity of the pupillary light reflex in both rd1 and rd10 mice, reflecting the prominent role of rod-cone input in generating the response. In contrast, there were marked differences in the disease phenotype for a behavioral response to light termed negative masking - a suppression of motile activity in bright light. As previously observed in rd1 mice, retinal degeneration caused a pronounced increase in irradiance sensitivity of negative masking. However, this phenotype did not emerge in rd10 even well after effective end stage rod-cone degeneration (200 days of age).

Conclusions: : There was clearly an interaction of rod-cone degeneration and retinal maturation in determining phenotype of irradiance responses. Negative masking 'hypersensitivity' only arises when rod-cone input is absent during critical stages in retinal maturation. However, the limited difference in the pupillary light reflex of rd1 and rd10 mice, suggests degeneration-maturation interaction effects are determined by the type of irradiance coding circuit. Retinal circuit function studies are ongoing but we have identified differences in the effect of degeneration on overall retinal activity between rd1 and rd10 mice.

Keywords: retinal degenerations: cell biology • plasticity • development