Gene Therapy Preserves Retinal Structure and Function in a Mouse Model of -Associated Retinal Degeneration.

No treatment is available for nicotinamide mononucleotide adenylyltransferase 1 ()-associated retinal degeneration, an inherited disease that leads to severe vision loss early in life. Although the causative gene, , plays an essential role in nuclear nicotinamide adenine dinucleotide (NAD) metabolism in tissues throughout the body, -associated disease is isolated to the retina. Since this condition is recessive, supplementing the retina with a normal copy of should protect vulnerable cells from disease progression.

In Vivo Assessment of Potential Therapeutic Approaches for USH2A-Associated Diseases.

Mutations in USH2A gene account for most cases of Usher syndrome type II (USH2), characterized by a combination of congenital hearing loss and progressive vision loss. In particular, approximately 30% of USH2A patients harbor a single base pair deletion, c.2299delG, in exon 13 that creates a frameshift and premature stop codon, leading to a nonfunctional USH2A protein.

An Experimental Animal Model of Photodynamic Optic Nerve Head Injury (PONHI).

Purpose: Anterior ischemic optic neuropathy (AION) is the most common cause of non-glaucomatous optic nerve head (ONH) injury among older adults. AION results from a sudden ischemic insult to the proximal portion of the optic nerve, typically leading to visual impairment. Here, we present an experimental model of photodynamically induced ONH injury that can be used to study neuroprotective modalities.

Photoreceptor rescue by an abbreviated human RPGR gene in a murine model of X-linked retinitis pigmentosa.

The X-linked RP3 gene codes for the ciliary protein RPGR and accounts for over 10% of inherited retinal degenerations. The critical RPGR-ORF15 splice variant contains a highly repetitive purine-rich linker region that renders it unstable and difficult to adapt for gene therapy. To test the hypothesis that the precise length of the linker region is not critical for function, we evaluated whether adeno-associated virus-mediated replacement gene therapy with a human ORF15 variant containing in-frame shortening of the linker region could reconstitute RPGR function in vivo.