MAMMALIAN RETINAL-PIGMENT EPITHELIAL-CELLS IN-VITRO RESPOND TO THE NEUROKINES CILIARY NEUROTROPHIC FACTOR AND LEUKEMIA INHIBITORY FACTOR

We examined whether primary cultures of rat retinal pigment epithelial (RPE) cells and RPE cells of an immortalized rat cell line, BPEI-1, w ould be responsive to the neurokines ciliary neurotrophic factor (CNTF ) and leukemia inhibitory factor (LIF), which are known to be potent t rophic factors for neuronal cells. Primary RPE cell cultures were char acterized by indirect immunofluorescence and exhibited positive immuno reactivity for RET-PE2, a monoclonal antibody that recognizes RPE cell s, and for the intermediate filaments cytokeratin and vimentin. The su rvival of cultured RPE cells in serum-free defined medium in the prese nce of CNTF or LIF was investigated during a 0- to 5-day period. Both CNTF and LIF, at concentrations of 1-50 ng/mL (4-200 pM), markedly enh anced RPE cell survival. Bromodeoxyuridine labelling of RPE cells reve aled an increased mitotic activity in cell cultures treated with eithe r CNTF or LIF in comparison to untreated serum-free cultures. Increase s in cell survival and proliferation after neurokine treatment were al so observed with the BPEI-1 cell line. However, in comparison to the p rimary RPE cultures, LIF was more effective than CNTF in promoting sur vival of the cell line over a 5-day treatment period. These studies de monstrate that the neurokines CNTF and LIF are potent trophic factors for mammalian RPE cells in vitro and may serve as candidate therapeuti c agents in degenerative conditions that affect the retina and RPE.