Inherited retinal degenerations: therapeutic prospects.
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.
Delyfer
Marie-Noëlle
MN
Laboratoire de Physiopathologie Cellulaire et Moléculaire de la Rétine - Inserm U 592 - Université Pierre et Marie Curie. Hôpital Saint-Antoine, 75571 Paris Cedex 12, France.
Léveillard
Thierry
T
Mohand-Saïd
Saddek
S
Hicks
David
D
Picaud
Serge
S
Sahel
José-Alain
JA
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002118:Calcium / Q000037:antagonists & inhibitors; D002470:Cell Survival; D017690:Cell Transplantation; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy; D006133:Growth Substances / Q000627:therapeutic use; D006801:Humans; D017949:Retinal Cone Photoreceptor Cells / Q000254:growth & development / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology / Q000637:transplantation; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014815:Vitamins / Q000627:therapeutic use
D006133:Growth Substances; D014815:Vitamins; D002118:Calcium