Investigating retinitis pigmentosa: A laboratory scientist's perspective

A decade's search for the molecular basis of retinitis pigmentosa (RP) has uncovered an unexpected genetic heterogeneity. These experimental results raise again the fundamental question concerning the pathogenesis of RP: mutations in a number of different genes all result in a similar phenotype of the disease - the gradual loss of photoreceptors. At the very least, this genetic heterogeneity allows us to make one important inference: it is cellular mechanisms other than the genetic defect alone which bring on the symptoms and clinical course typical of RP. Furthermore, once they have begun to express themselves, this multitude of RP-inducing mutations seem to converge into a common set of cellular mechanisms that eventually lead to photoreceptor death. In those cases where the RP-inducing mutation is in a rod photoreceptor-specific gene, cell-cell interactions may lead to the death of normal cone photoreceptors. RP researchers are now confronted by three related challenges: to pinpoint the immediate physiologic effects of the various RP-inducing mutations; to identify the mechanisms directly causing photoreceptor death; and, to delineate the link between a specific mutation and the direct cause of photoreceptor death.

Duke Scholars

Author Fulton Wong Ophthalmology