Therapeutic Window of AAV-SIRT1 Gene Therapy in Mouse Models of Optic Nerve Degeneration

Purpose

Optic neuropathies involve progressive loss of retinal ganglion cells (RGCs) and their axons, leading to irreversible vision deficits. While pretreatment with drugs or gene therapy that upregulate sirtuin 1 (SIRT1), an NAD⁺-dependent deacetylase, has shown neuroprotective effects, its effectiveness when administered after disease onset remains uncertain. We investigated whether adeno-associated virus (AAV)-mediated SIRT1 overexpression in RGCs can provide post-onset neuroprotection in preclinical models of optic neuropathy.