Preclinical evaluation of ALDH1A1 gene therapy for the prevention of diabetic retinopathy

The role of ALDH1a1 in detoxifying ACR was assessed both in vitro and in vivo. To model Müller cell dysfunction in DR, QMMuC-1 murine Müller cells were exposed to varying doses of ACR.

The effects of ACR on inflammatory gene expression and markers of Müller cell dysfunction were measured, along with the potential of AAV2.ALDH1A1 therapy to prevent ACR-induced damage. In vivo, male Sprague-Dawley rats were divided into four groups: nondiabetic, streptozotocin (STZ)-induced diabetic, and STZ-induced diabetic rats treated with either control virus (AAV2.eGFP) or AAV2.ALDH1A1. ACR significantly impacted Müller cells, with high concentrations inhibiting cell proliferation and causing cell death, while lower concentrations led to FDP-lysine accumulation and increased inflammatory cytokine expression.