# Retinal Pigment Epithelium‐Targeting Gene Therapy Corrects Ocular Symptoms in Mouse and Rat Models of Oculocutaneous Albinism Type I

## TL;DR

A gene therapy targeting the retina successfully corrected eye issues in mouse and rat models of a type of albinism.

## Contribution

A long-term, safe, and effective RPE-targeted gene therapy for Oculocutaneous Albinism Type I is demonstrated.

## Key findings

- AAV8.hRPE65p.hTYRco gene therapy restored tyrosinase and melanin in retinal pigment epithelium.
- Retinal structure and visual function were preserved for up to 12 months with no toxicity.
- Suprachoroidal delivery of the therapy improved ocular dysfunction in Wistar rats for at least 12 months.

## Abstract

Oculocutaneous albinism (OCA) represents a genetically heterogeneous autosomal recessive condition marked by reduced melanin production in cutaneous and ocular tissues. This disorder primarily arises from mutations in the TYR gene, which encodes tyrosinase—the rate‐limiting enzyme in melanogenesis. Such genetic defects lead to impaired or absent tyrosinase activity, consequently causing melanin deficiency. Currently, no curative treatment exists for OCA1. In this study, we investigated the efficacy of AAV vector‐based gene therapy in two murine models of OCA1, evaluating its potential as a therapeutic intervention. B6 albino mice were injected with three AAV8 vectors containing distinct promoters at different dosages, among which AAV8.hRPE65p.hTYRco showed the best therapeutic effect at a dose of 1 × 109 GC/eye. This RPE‐targeted strategy restored the expression of functional tyrosinase and melanin deposition in the RPE layer. More importantly, the retinal structure and visual function were maintained at nearly normal levels for up to 12 months, with no obvious toxicity. In addition, we demonstrated that the suprachoroidal cavity delivery of AAV8.hRPE65p.hTYRco restored the expression of tyrosinase and relieved ocular dysfunction in Wistar rats for at least 12 months. The results revealed a long‐term, effective, safe strategy for treating OCA1.

RPE‐targeted gene therapy restored melanin expression and relieved ocular dysfunction. By optimizing the injection method, a wider range of melanin expression and better therapeutic effects have been achieved.