Implication of protein carboxymethylation in retinal pigment epithelial cell chemotaxis

Two chemoattractants for retinal pigment epithelial (RPE) cells, fibronectin (FN) and platelet-derived growth factor (PDGF) were found to enhance protein carboxymethylation mediated by S-adenosyl-L-methionine in RPE cells measured by [3H]methanol hydrolyzed from TCA precipitable protein methyl esters labelled with [3H]methionine. The effect was rapid, peaking at 2 min when [3H]methanol production was enhanced 120% by FN and 150% by PDGF. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 10 microM), adenosine (100 microM), and L-homocysteine thiolactone (100 microM) inhibited FN-induced carboxymethylation by 60%, and PDGF-induced carboxymethylation by 59%. In modified Boyden chamber assays, the combination of EHNA (10 microM), adenosine (100 microM), and L-homocysteine thiolactone (100 microM) markedly inhibited FN-induced chemotaxis by 88% and PDGF-induced chemotaxis by 93%). Migration of RPE cells has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR). Inhibition of protein carboxymethylation may provide a new target in the development of pharmacologic therapy for PVR.