Hereditary degenerative retinopathies: optimism for somatic gene therapy

Abstract

Retinitis pigmentosa comprises a large and exceptionally heterogeneous group of hereditary disorders of the retina. As a result of an extensive investigation around the world, primary genetic lesions have been described in many genes. Some of these genes encode enzymes that are involved in the signal transduction pathway. On the basis of in vitro functional assays and standard transgenic and knock-out experiments, it has been proposed that normal cell functions are disrupted because of an abnormal protein-folding and metabolic errors or structural defects in the membrane. This ultimately leads to a gene-mediated cell death known as apoptosis. Various gene transfer approaches using mouse models further suggest that the degeneration can be rescued to some extent. Although many questions remain to be answered, investigations during the last 10 years have enormously increased our understanding of this exceptionally heterogeneous disorder and give hope for an effective gene therapy and a possible cure.