Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS rats.

ABSTRACT:

Purpose

The absence of Mertk in RCS rats results in defective RPE phagocytosis, accumulation of outer segment (OS) debris in the subretinal space, and subsequent death of photoreceptors. Previous research utilizing Mertk gene replacement therapy in RCS rats provided proof of concept for treatment of this form of recessive retinitis pigmentosa (RP); however, the beneficial effects on retinal function were transient. In the present study, we evaluated whether delivery of a MERTK transgene using a tyrosine-mutant AAV8 capsid could lead to more robust and longer-term therapeutic outcomes than previously reported.

Methods

An AAV8 Y733F vector expressing a human MERTK cDNA driven by a RPE-selective promoter was administrated subretinally at postnatal day 2. Functional and morpholo

SUBMITTER: Deng WT 

PROVIDER: S-EPMC3995567 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature