Retinal pigment epithelial cells direct spatial orientation, survival and differentiation of photoreceptors.

GERMAN L; BUZZI E; RODRÍGUEZ-BOULAND ENRIQUE; ROTSTEIN N; POLITI L

Pinamar, Buenos Aires, Argentina,

Congreso; X Congress PABMB, XLI Annual Meeting of the Argentine SAIB and XX Annual Meeting of SAN; 2005

Retinal pigment epithelial cells direct spatial orientation, survival and differentiation of photoreceptors German, Lorena1; Buzzi, Edgardo1; Rotstein, Nora1, Rodríguez Boulan, Enrique2 and Politi, Luis1. 1,Instituto de Investigaciones Bioquímicas, UNS-CONICET. 8000 Bahía Blanca, Argentina; 2,M. Dyson Vis. Res. Inst., Cornell Univ, NY, USA. E-mail: olgerman@criba.edu.ar We have previously shown that retinal pigment epithelial cells (ARPE-19) partially prevented photoreceptor apoptosis in neuron-ARPE-19 cocultures lacking photoreceptor trophic factors. Addition of photoreceptor trophic factors, docoxahexaenoic acid (DHA) and glial cell-derived neurotrophic factor (GDNF) to cocultures showed no additive protective effect. Epithelial cells and DHA enhanced photoreceptor differentiation, stimulating the development of apical processes and opsin correct localization in these processes. DHA increased opsin expression in cocultures, while epithelial cells did not. We have previosuly described that epithelial cells in cocultures promote a rapid spatial reorganization, which ends with the apical face of epithelial cells exposed to neurons, as occurs in vivo. Addition of a  metalloproteinase inhibitor (TIMP-1) blocked the ability of  epithelial cells to separate neurons from their substrate, without affecting the outgrowth of lamellipodia, suggesting that metalloproteinases are involved in the reorganization process. These results suggest that epithelial cells are crucial for photoreceptor development and orientation, and thus essential for developing the final retina structure.