Novel Combinatory Approaches to Repair Visual System after Optic Nerve Damage

摘要: Abstract : Background: Death of retinal ganglion cells (RGCs) and poor regeneration are major obstacles for treating traumatic optic neuropathy after road accident, falls or combat blasts. Optic nerve from many long-term surviving RGCs, reconnecting the brain could potentially restore vision injury. We previously determined that deletion two genes, PTEN SOCS3 induces regeneration. On other hand, genetic modification CHOP XBP1 in RGCs render them highly resistant to injury-induced death. Objective/hypothesis: will use knockout mice therapeutically relevant short hairpin RNA (shRNA) approaches determine combined effects targeting PTEN/SOCS3 CHOP/XBP1 on RGC survival In addition, we examine integrity functions these genes using pattern electroretinogram (PERG). hypothesize strategies target further enhance regeneration, animals exhibit normal physiological responses. Specific Aims/Study Design: Aim 1: Use PTEN/SOCS3/CHOP receive AAV-assisted over-expression XBP1, followed by crush injury assessment 2: Integrity be evaluated PERG. 3: Optimize shRNA approach promote PTEN, knocked down alone combination shRNAs improve Relevance: Military personnel run a high risk incurring ocular damage. This proposal probe interventions rescue dying neurons vision, with potential administered clinic battlefield.