Neuroprotective properties of sigma-1 Receptor in Retinal Ganglion cells from Optic Crush Model

Glaucoma is a group of neurodegenerative disorders that lead to the death of the retinal ganglion cells (RGC), optic nerve damage, and may ultimately cause blindness. Elevated intraocular pressure (IOP) is one of the major contributors to glaucoma1. As a result, the majority of treatments available target lowering IOP, as a therapy for glaucoma2. Purpose: Studying the neuroprotection of RGCs is important to provide alternative therapies for pro-survival which mitigates RGC death and irreversible optic nerve damage. This study will investigate the sigma-1 receptor as an alternate additional therapeutic target to provide protection of Retinal ganglion cells (RGCs) and possible treatment for glaucoma. Hypothesis: It is hypothesized that the sigma-1 receptor (σ-1r) offers neuroprotection to retinal ganglion cells, therefore, it will restore RGCs and mitigate cell death. Methods: Treatment groups: wild type mice and σ-1r KO mice. Transfected mice with AAV2-σ-1r vector in order to induce overexpression of sigma-1 receptor (σ-1r), activated σ-1r through agonist- pentazocine, afterward induced injury via Optic Nerve Crush (ONC) protocol, then assessed RGC function and survival. Expression of σ-1r assessed using immunohistostaining & western blot analysis. Pattern Electrocardiogram (PERG) was used to assess visual function of mice retina pre and post- ONC. Adobe Photoshop software was used post retina staining and flat mount to assess the density of RGCs. Results & Conclusion: When σ-1r was activated and overexpressed, retinal ganglion cells death was mitigated in σ-1r knock out mice. This data suggests that σ-1r has neuroprotective functions to the retinal ganglion cells. Studying the mitigation of retinal ganglion cell death may be beneficial as an alternate target in the treatment of Glaucoma and other optic neuropathies.