Hyalocytes inhibit retinal pigment epithelium cell proliferation in vitro

Under pathological conditions such as retinal detachment or proliferative vitreoretinopathy, the normally quiescent retinal pigment epithelium (RPE) may proliferate. We investigated whether hyalocytes, endogenous to the vitreous, might play a role in modulating the proliferation of RPE cells in vitro. We cultured hyalocytes from bovine eyes and RPE cells from human eyes. RPE cell proliferation was determined by [3H]-thymidine incorporation following incubation with hyalocyte-conditioned media (HCM). HCM inhibited RPE cell proliferation with no effect on cell viability as based on trypan blue exclusion. This inhibition was partially antagonized by a specific neutralizing antibody against transforming growth factor-beta (anti-TGF beta antibody). Fractionation of HCM into low- and high-molecular-weight components showed inhibition of RPE cell proliferation in both fractions, suggesting that there may be multiple inhibitors. Whereas protease inhibition of HCM did not alter the inhibition of RPE cell proliferation, acid activation of HCM, which causes activation of latent TGF beta, enhanced its inhibitory effect. These data suggest that cultured hyalocytes secrete active and latent TGF beta and that this accounts for a portion of their inhibitory effect on RPE cell proliferation in vitro.