Abstract
Purpose :
The fibrotic proliferative reaction contributes to the loss of vision associated with retinal diseases such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy diseases (PVD). The epithelial-mesenchymal transition in retinal pigment epithelial (RPE) cells and extra cellular matrix such as collagen play a key role in the fibrotic reaction. We examined the effect of retinoic acid receptor-α (RAR-α) in collagen gel contraction mediated by mouse RPE cells.
Methods :
Primary mouse RPE cells cultured in a type I collagen gel were incubated with or without transforming growth factor-β2 (TGF-β2) and the RAR-α agonist Am580. Collagen gel contraction was determined by measurement of gel diameter. Expression of α–smooth muscle actin (α-SMA), Tissue Inhibitor of Metalloproteinase (TIMP)-1, paxillin was examined by immunoblot analysis. Interleukin-6 (IL-6) secretion was measured with immunoassays.
Results :
The RAR-α agonist Am580 inhibited TGF-β2-induced collagen gel contraction mediated by the RPE cells in a concentration- and time-dependent manner. Expression of the mesenchymal markers α-SMA, TIMP-1 and paxillin, the release of IL-6 induced by TGF-β2 were inhibited by Am580.
Conclusions :
Our observations suggest that RAR-α signaling may be effective for effect of EMT in RPE cells, and play a key role in the pathogenesis of fibrotic proliferative retinal disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.