Current Concepts in the Treatment of Retinitis Pigmentosa

Abstract

Inherited retinal degenerations, including retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), affect 1 in 4000 individuals in the general population. A majority of the genes which are mutated in these conditions are expressed in either photoreceptors or the retinal pigment epithelium (RPE). There is considerable variation in the clinical severity of these conditions; the most severe being autosomal recessive LCA, a heterogeneous retinal degenerative disease and the commonest cause of congenital blindness in children. Here, we discuss all the potential treatments that are now available for retinal degeneration. A number of therapeutic avenues are being explored based on our knowledge of the pathophysiology of retinal degeneration derived from research on animal models, including: gene therapy, antiapoptosis agents, neurotrophic factors, and dietary supplementation. Technological advances in retinal implant devices continue to provide the promise of vision for patients with end-stage disease.

Mathematical models of retinitis pigmentosa: The oxygen toxicity hypothesis

“…Treatment would need to be maintained throughout the lifetime of the patient, otherwise degeneration would resume. Antioxidants and trophic factors could be supplied over the long-term using either encapsulated cell technology or ocular gene therapy (see, for example, Dong et al, 2006;Musarella and MacDonald, 2011;Orosz et al, 2004;Tao, 2006;Tao et al, 2002;Wen et al, 2012). If treatment could be targeted to specific regions of the retina, our results suggest that the unstable peripheral and para/perifoveal regions should be targeted, as they are most susceptible to hyperoxic damage.…”

“…RP is the most common inherited retinal degeneration, with a prevalence (in its nonsyndromic form) of 1 in 4000, corresponding to a total of 1.5 million affected individuals worldwide (Hamel, 2006;Hartong et al, 2006;Shintani et al, 2009). At present no treatments are clinically available either to slow its progression or reverse its effects (Musarella and MacDonald, 2011). In this paper, we investigate the prospective role of oxygen toxicity (or hyperoxia) in the progression of RP.…”

Retinitis Pigmentosa in Northern Sweden - From Gene to Treatment

“…Gene therapy, which replaces or turns off the mutant disease-causing gene, represents another option for treatment. Several years of basic research of RPE65-Lebers congenital amaurosis, a retinal disease affecting the visual cycle, by several independent research groups, resulted in clinical trials of human gene therapies during recent years, demonstrating short-term evidence of visual gain (Jacobson & Cideciyan, 2010;Musarella & MacDonald, 2011). Therefore, we suggest that for treatment of BD patients, gene therapy is the most promising option among other concepts in the treatment of retinitis pigmentosa.…”

Spotlight on childhood blindness

“…Advances in therapy for LCA Ocular gene therapy has been tried with success in mice, dogs, and, most recently, humans (15). It is most advanced for LCA caused by mutations in RPE65.…”