transforming-growth-factor-beta and Wet-Macular-Degeneration

Age-related macular degeneration (AMD) is one of the major causes of irreversible blindness among aging populations in developed countries and can be classified as dry or wet according to its progression. Wet AMD, which is characterized by angiogenesis on the choroidal membrane, is uncommonly seen but more severe. Controlling or completely inhibiting the factors that contribute to the progression of events that lead to angiogenesis may be an effective strategy for treating wet AMD. Emerging evidence has shown that transforming growth factor-β (TGF-β) signaling plays a significant role in the progression of wet AMD. In this review, we described the roles of and changes in TGF-β signaling in the development of AMD and discussed the mechanisms of the TGF-β superfamily in choroidal neovascularization (CNV) and wet AMD, including the modulation of angiogenesis-related factors, inflammation, vascular fibrosis, and immune responses, as well as cross-talk with other signaling pathways. These remarkable findings indicate that TGF-β signaling is a potential target for wet AMD treatment.

Topics: Angiogenesis Inhibitors; Choroidal Neovascularization; Cytokines; Disease Progression; Humans; Inflammation Mediators; Signal Transduction; Transforming Growth Factor beta; Wet Macular Degeneration

The transforming growth factor-beta (TGFB) plays an essential role in the pathogenesis of some ophthalmologic diseases, including neovascular age-related macular degeneration (nAMD) and proliferative vitreoretinopathy (PVR). TGFB activates the transcription factors SMAD2 and SMAD3 via the TGFB receptor, which together activate several genes, including VEGFA. TGFB treated ARPE-19 cells show an increased proliferation rate and undergo epithelial to mesenchymal transition (EMT). Since microRNAs (miRNAs) are capable of inhibiting the translation of multiple genes, we screened for miRNAs that regulate the TGFB signalling pathways at multiple levels. In this study, we focused on two miRNAs, miR-302d and miR-93, which inhibit TGFB signalling pathway and therefore TGFB-induced EMT transition as well as VEGFA secretion from ARPE-19 cells. Furthermore, we could show that both miRNAs can retransform TGFB-stimulated mesenchymal ARPE-19 cells towards the morphological epithelial-like state. Taken together, transient overexpression of these miRNAs in RPE cells might be a promising approach for further translational strategies.

Topics: Blotting, Western; Cell Line; Enzyme-Linked Immunosorbent Assay; Epithelial-Mesenchymal Transition; Gene Expression Regulation; Humans; MicroRNAs; Retinal Pigment Epithelium; RNA; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Wet Macular Degeneration