Integrative properties of retinal ganglion cell electrical responsiveness depend on neurotrophic support and genotype in the mouse

Early stages of glaucoma and optic neuropathies are thought to show inner retina remodeling and functional changes of retinal ganglion cells (RGCs) before they die. To assess RGC functional plasticity, we investigated the contrast-gain control properties of the pattern electroretinogram (PERG), a sensitive measure of RGC function, as an index of spatio-temporal integration occurring in the inner retina circuitry subserving PERG generators. We studied the integrative properties of the PERG in mice exposed to different conditions of neurotrophic support. We also investigated the effect of genotypic differences among mouse strains with different susceptibility to glaucoma (C57BL/6J, DBA/2J, DBA/2.Gpnmb+). Results show that the integrative properties of the PERG recorded in the standard C57BL/6J inbred mouse strain are impaired after deficit of neurotrophic support and partially restored after exogenous neurotrophic administration. Changes in PERG amplitude, latency, and contrast-dependent responses differ between mouse strains with different susceptibility to glaucoma. Results represent a proof of concept that the PERG could be used as a tool for in-vivo monitoring of RGC functional plasticity before RGC death, the effect of neuroactive treatments, as well as for high-throughput tool for phenotypic screening of different mouse genotypes.