Retinal pigment epithelium-stromal interactions modulate hyaluronic acid deposition

Hyaluronic acid (HA) is a major component of the extracellular matrix (ECM) and is particularly prominent in various structures of the eye. Choroidal mesenchymal fibroblasts (CHM) and fetal retinal pigment epithelial (fRPE) cells were cultured individually and in cocultivation, as a paradigm for ocular stromal-epithelial interactions. Such interactions are thought to be a key mechanism for the modulation of the ECM and of HA deposition in the region of Bruch's membrane and related structures. In cocultivation, increased levels of HA production were observed, more than the sum of the two cell types grown individually. Conditioned medium from fRPE cultures placed over CHM cells was able to enhance production in such cells several-fold, demonstrating that cell-cell contact was not needed for this enhanced production. On the other hand, when conditioned medium from CHM fibroblasts was added to the fetal RPE cells, no increase in HA production was observed. A soluble HA-stimulating factor apparently released by fRPE cells in a paracrine manner enhanced HA production in CHM cells. The fRPE cell-conditioned media was unable to exert this effect on the fRPE cells themselves. The fRPE cells may lack the appropriate receptor. Alternatively, they may not have the biosynthetic machinery for augmented HA production.