Hyalocytes synthesize and secrete inhibitors of retinal pigment epithelial cell proliferation in vitro

Arch Ophthalmol. 1996 Jun;114(6):731-6. 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 hyalocyte-conditioned medium was performed, including blocking experiments with a neutralizing antibody to transforming growth factor-beta 2 (TGF-beta) and proliferation assays that used MV-1-Lu mink lung epithelial cells. Northern blots were done to asses hyalocyte expression of TGF-beta 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-beta. Northern blots of hyalocyte RNA demonstrated the presence of messenger RNA for TGF-beta 2. These data suggest that TGF-beta 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-beta.

Conclusions: Hyalocyte-conditioned medium inhibits RPE cell proliferation in vitro through TGF-beta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Cattle
  • Cell Division / drug effects
  • Cell Line
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • DNA / biosynthesis
  • DNA Replication / drug effects
  • Epithelium / drug effects
  • Growth Inhibitors / biosynthesis
  • Growth Inhibitors / metabolism
  • Growth Inhibitors / pharmacology*
  • Humans
  • Immunoenzyme Techniques
  • Lung / cytology
  • Lung / drug effects
  • Macrophages / metabolism*
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / drug effects*
  • RNA, Messenger / biosynthesis
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology*
  • Vitreous Body / cytology*


  • Culture Media, Conditioned
  • Growth Inhibitors
  • RNA, Messenger
  • Transforming Growth Factor beta
  • DNA