CILIARY NEUROTROPHIC FACTOR BLOCKS ROD PHOTORECEPTOR DIFFERENTIATION FROM POSTMITOTIC PRECURSOR CELLS IN-VITRO

The development of photoreceptors in the mammalian retina is thought t o be controlled by extrinsic signals. We have shown previously that ci liary neurotrophic factor (CNTF) potently inhibits photoreceptor diffe rentiation in cultures of rat retina. The present study analyzes which developmental processes are affected by CNTF. Rod differentiation as determined by opsin and re coverin immunocytochemistry was effectively blocked by CNTF and leukemia inhibitory factor, but not by other neur otrophic agents tested. CNTF did not influence proliferation, cell dea th, or survival, and had no effect on the downregulation of nestin imm unoreactivity in progenitor cells. Opsin-positive rods could be revert ed to an opsin-negative state initially, but became unresponsive to CN TF later. No compensatory increase in the number of other cell types w as observed. Application of neutralizing antibodies against CNTF revea led that rod development was partially blocked by an endogenous CNTF-l ike molecule in control cultures. Our results suggest that CNTF can ac t as a specific negative regulator of rod differentiation. Its action on photoreceptor precursor cells could serve to synchronize the matura tion of photoreceptors, which are born over an extended period of time . Together with other stimulatory signals, CNTF may thus control the t emporally and numerically correct integration of photoreceptors into t he retinal network.