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June 1996

Hyalocytes Synthesize and Secrete Inhibitors of Retinal Pigment Epithelial Cell Proliferation In Vitro

Author Affiliations

From The Wilmer Ophthalmological Institute, The Johns Hopkins Hospital, Baltimore, Md (Drs Lazarus, Schoenfeld, Fekrat, Chen, Vinores, and Campochiaro, Messrs Cohen and Hackett, and Ms Carol); and Anheuser-Busch Eye Institute, Department of Ophthalmology, St Louis (Mo) University School of Medicine (Dr Hageman).

Arch Ophthalmol. 1996;114(6):731-736. doi:10.1001/archopht.1996.01100130723015

Background:  Retinal pigment epithelial (RPE) cells that enter the vitreous in pathologic conditions, such as retinal detachment, may proliferate and contribute to the formation of epiretinal membranes.

Objective:  To study whether hyalocytes, endogenous vitreous cells, play a role in modulating the proliferation of RPE cells.

Methods:  Cell proliferation was measured by tritiated thymidine incorporation in density-arrested human RPE cells after incubation with media that had been conditioned by cultured bovine hyalocytes. Preliminary characterization of inhibitory activity in hyalocyteconditioned medium was performed, including blocking experiments with a neutralizing antibody to transforming growth factor-β2 (TGF-β) and proliferation assays that used MV-1-Lu mink lung epithelial cells. Northern blots were done to assess hyalocyte expression of TGF-β messenger RNA.

Results:  Hyalocyte-conditioned medium inhibited tritiated thymidine incorporation in RPE cells and MV-1-Lu mink lung epithelial cells in the presence or absence of serum or protease inhibitors. A portion of the inhibitory activity was neutralized by an antibody directed against TGF-β. Northern blots of hyalocyte RNA demonstrated the presence of messenger RNA for TGF-β2. These data suggest that TGF-β is responsible for a portion of the inhibitory activity secreted by hyalocytes. Additional inhibitory activity is attributable to one or more low-molecular-weight molecules distinct from TGF-β.

Conclusion:  Hyalocyte-conditioned medium inhibits RPE cell proliferation in vitro through TGF-β and at least one other molecule. Production of these factors by hyalocytes in vivo could provide a deterrent for epiretinal membrane formation that may be perturbed under pathologic conditions.

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