In vivo imaging of the light response in mouse retinal ganglion cells based on a neuronal activity-dependent promoter

Abstract

Diseases of the retinal ganglion cells (RGCs) are an important cause of blindness, yet the light response of individual RGCs is difficult to assess in vivo, particularly in mammals, due to a lack of effective methods. We report a simple in vivo platform for imaging the light response of mouse RGCs based on a fluorescent reporter-tagged enhanced synaptic activity-responsive element (E-SARE) that mediates neuronal activity–dependent gene transcription. When E-SARE-driven d2Venus, packaged into an AAV vector, was injected intravitreally, light-responsive retinal neurons expressing d2Venus were visible at single-cell resolution using confocal ophthalmoscopy. Immunohistological assessment identified the majority of these cells as RGCs. In a murine model of RGC injury, the number of d2Venus-positive cells was correlated with the amplitude of light-induced responses and with visual acuity, measured electrophysiologically at the visual cortex, indicating that the vector can be used as a tool to assess visual function in RGCs. The platform described herein allows a simple in vivo assessment of RGC function, which should help basic research into the mechanisms of RGC death and the development of treatments for diseases involving the RGCs.