Population Of Melanopsin-expressing Retinal Ganglion Cells In Aging Wildtype And Rodless/coneless Mice: A Detailed Quantitative And Topographical Analysis

Abstract

Purpose: : Outer retinal degeneration in the rd/rd mouse model leads to retinal ganglion cell loss (at ~1 yr of age). However old mice (>2 yrs) lacking both rods and cones (rd/rd cl) and wildtypes maintain melanopsin-mediated responses to light. The density of melanopsin cells declines with advanced age in both wildtypes and rd/rd cl independently of retinal degeneration. Here we analyse the total numbers and the distribution of intrinsically photosensitive melanopsin positive ganglion cells in the retina during advanced aging (1-2.5 years) in wildtype mice and compare it to aging congenic rd/rd cl mice.

Methods: : Mice were sacrificed at 1, 1.5 and 2.5 yrs of age (n=3-4 per group), retinae dissected as flatmounts, and melanopsin detected with immuno-fluorescence, some retinae were also co-labelled with a general ganglion cell marker Brn3a. Detailed maps of the retina were obtained using a Zeiss LSM 710 confocal microscope and the whole population of melanopsin positive cells was quantified.

Results: : Melanopsin cells were found distributed across the retinae at all ages and in all genotypes and were not found to be Brn3a positive. At 1 yr the wildtypes and rd/rd cl have similar total numbers of melanopsin cells, however by 1.5 yrs the rd/rd cl has fewer cells in comparison to age-matched wildtypes (P<0.05). By 2.5 yrs the wildtypes have fewer melanopsin cells than they did at 1 yr with counts at a similar level to the rd/rd cl at 1.5 yrs.

Conclusions: : Outer retinal degeneration causes the melanopsin cell population to decrease at a faster rate however advanced aging in the wildtype leads to a similar loss of melanopsin positive cells. The maintenance of relatively un-attenuated irradiance detection responses into old age despite this reduction suggests there may be some compensatory plasticity enhancing signaling of the melanopsin system in old age.

Keywords: ganglion cells • retina • visual cortex