Inherited retinal degenerations: therapeutic prospects

Abstract

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerative diseases, characterized by the progressive death of rod and cone photoreceptors. A tremendous genetic heterogeneity is associated with the RP phenotype. Most mutations affect rods selectively and, through an unknown pathway, cause the rod cells to die by apoptosis. Cones, on the other hand, are seldom directly affected by the identified mutations, and yet, in many cases, they degenerate secondarily to rods, which accounts for loss of central vision and complete blindness. Many animal models of RP are available and have led to a better understanding of the disease and to the development of therapeutic strategies aimed at curing the specific genetic disorder (gene therapy), slowing down or even stopping the process of photoreceptor degeneration (growth factors or calcium blockers applications, vitamin supplementation), preserving the cones implicated in the central visual function (identification of endogenous cone viability factors) or even replacing the lost cells (transplantation, use of stem or precursor cells). Still, many obstacles will need to be overcome before most of these strategies can be applied to humans. In this review, we describe the different therapeutic strategies being studied worldwide and report the latest results in this field.

Exacerbation of retinal degeneration in the absence of alpha crystallins in an in vivo model of chemically induced hypoxia

“…Animal models of retinal degeneration have provided a better understanding of disease pathogenesis and have led to the development of novel therapeutic strategies (Delyfer et al, 2004). Many of these animal studies stem from genetically distinct mouse strains, such as the rd mouse, which possesses a mutation of rod-specific phosphodiesterase (Bowes et al, 1990;Jimenez et al, 1996).…”

BDNF-treated retinal progenitor sheets transplanted to degenerate rats: Improved restoration of visual function

“…These studies have also provided investigators with information to assist in optimizing therapeutic strategies aimed at preventing visual loss and or restoring lost vision. Therapeutic interventions in animal models, including growth factor treatment, gene therapy, retinal prosthetics and retinal cell transplantation, have been presumed to improve visual sensitivity Seiler, 2002, 2004;Chaum, 2003;Delyfer et al, 2004;Loewenstein et al, 2004;Lund et al, 2001) by delaying the progression of the disease and/or by rescuing the remaining host photoreceptors. Some studies of retinal sheet transplants have suggested that transplanted photoreceptors may also contribute directly to the visual restoration Seiler et al, 2005a).…”

Excessive Activation of Poly(ADP-Ribose) Polymerase Contributes to Inherited Photoreceptor Degeneration in the Retinal Degeneration 1 Mouse

“…Over 160 different mutations, encompassing genes coding for proteins with remarkably diverse functions, are known to cause RP (www.sph.uth.tmc.edu/retnet). Surprisingly, however, the pathological mechanisms behind the degeneration have not been resolved for any of these mutations and effective RP treatment is lacking (Delyfer et al, 2004).…”