An osmolarity dependent mechanism partially ameliorates retinal cysts and rescues cone function in a mouse model of X-linked retinoschisis.

Introduction: X-linked retinoschisis (XLRS) is a vitreoretinal dystrophy caused by gene mutations which disrupt retinoschisin-1 (RS1) function. Vital for retinal architecture, the absence of functional RS1 leads to the development of intraretinal cysts. Intravitreal injection of a gene therapy for treating XLRS caused ocular inflammation in high dose groups in a phase I/II clinical trial.

The dose-response relationship of subretinal gene therapy with rAAV2tYF-CB-h in a mouse model of X-linked retinoschisis.

Purpose: X-linked retinoschisis (XLRS), due to loss-of-function mutations in the retinoschisin () gene, is characterized by a modest to severe decrease in visual acuity. Clinical trials for XLRS utilizing intravitreal (IVT) gene therapy showed ocular inflammation. We conducted a subretinal dose-response preclinical study using rAAV2tYF-CB-h utilizing the knockout (-KO) mouse to investigate short- and long-term retinal rescue after subretinal gene delivery.