The search for rod-dependent cone viability factors, secreted factors promoting cone viability.

During the last decade, numerous research reports have considerably improved our knowledge of the pathophysiology of retinal degenerations. Three non-mutually exclusive general areas dealing with therapeutic approaches have been proposed: gene therapy, pharmacology and retinal transplantations. The observation that cone photoreceptors, even those seemingly unaffected by any described anomaly, die secondarily to rod disappearance related to mutations expressed specifically in the latter, led us to study the interactions between these two photoreceptor populations to search for possible causal links between rod degeneration and cone death. These in vivo and in vitro studies suggest that paracrine interactions between both cell types exist and that rods are necessary for continued cone survival. We have developed a protocol that is used to evaluate the potential of all sequences in a retinal library to generate a protective effect on cones from cone-enriched cultures from chicken embryo. The protocol of expression cloning is a systematic approach aimed at screening all genes normally expressed by retina. Since the role of cones in visual perception is essential, pending the identification of the factors mediating these interactions underway, rod replacement by transplantation and/or neuroprotection by trophic factors or alternative pharmacological means appear as promising approaches for limiting secondary cone loss in currently untreatable blinding conditions.