RETINOIC ACID PROMOTES DIFFERENTIATION OF PHOTORECEPTORS IN-VITRO

The results of several recent studies have demonstrated that cell comm itment and differentiation in the developing vertebrate retina are inf luenced by cen-cell interactions within the microenvironment. Retinoic acid has been shown to influence cell fates during development of the nervous system, and retinoic acid has been detected in the embryonic retina. To determine whether retinoic acid mediates the differentiatio n of specific neuronal phenotypes during retinal histogenesis, we trea ted dissociated cell cultures of embryonic and neonatal rat retina wit h varying concentrations of all-trans or 9-cis retinoic acid and analy zed the effects on cell fate using neuron and photoreceptor-specific a ntibodies. Addition of exogenous retinoic acid caused a dose-dependent , specific increase in the number of cells that developed as photorece ptors in culture throughout the period of retinal neurogenesis. In the same cultures, retinoic acid also caused a dose-dependent decrease in the number of cells that developed as amacrine cells. Also, results o f double-labeled immunohistochemical studies using bromodeoxyuridine d emonstrated that the primary effect of retinoic acid was to influence progenitor cells to develop as newly generated rod photoreceptors. Sin ce retinoic acid and at least one of the retinoic acid receptors (RAR alpha) have been localized to the developing neural retina, these resu lts suggest that retinoic acid may play a role in the normal developme nt of photoreceptor cells in vivo.