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S. Minchiotti, B. Stampachiacchiere, G. Ripandelli, B. Billi, A. Micera, A. Lambiase, S. Bonini; TGF–ß1 and NGF Involvement in Myofibroblast Differentiation and Survival in Human Idiopathic Epiretinal Membranes . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5506.
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Different cell types (including fibroblasts) have been demonstrated to play a major role in Epiretinal Membranes (ERMs) development and evolution. Fibroblasts differentiation into myofibroblasts (myoFBs) lead to hypertrophic scars and tissue contraction. Recently, we demonstrated that NGF other than TGF–ß plays a crucial role in fibroblast differentiation, survival, contraction and migration. The presence of myoFBs and the expression of TGF–ß1, NGF and NGF receptors were evaluated in both ERMs and vitreous and compared to controls.
Three epiretinal membranes and vitreous samples were obtained from patients at the time of vitrectomy for macular pucker, and 3 vitreous samples from cadaver eyes with no history of retinal disease (controls). Biochemical (Immunohistochemistry, Confocal analysis and Western blotting) and molecular (conventional RT–PCR) analyses were performed to identify α–SMA (a typical differentiation marker for myoFBs), TGF–ß1, NGF, and NGF receptors (trkA and p75) expression.
Immunohistochemistry showed the presence of myoFBs (α–SMA positive cells) in all idiopathic ERMs. Moreover, the presence of both α–SMA protein and mRNA was confirmed by Western blot and RT–PCR respectively. TGF–ß1, NGF, trkA and p75 protein and mRNA were also detected in ERMs. Confocal analysis demonstrated that TGF–ß1, NGF, trkA and p75 were expressed by myoFBs. In addition, TGF–ß1 protein levels were significantly increased in the vitreous of the patients affected by ERMs compared to controls (314.5±56.6pg/ml vs 207.5±46.7pg/ml; p<0.05), while NGF protein levels were decreased compared to vitreous controls (244.8±35.6pg/ml vs 385.5±46.7pg/ml; p<0.05).
The presence of α–SMA positive cells in idiopathic ERMs suggest a pathogenetic role of myoFBs during membrane contraction. This hypothesis is supported by the observation of an increased levels of TGF–ß1 in ERMs and vitreous. The decrease of NGF levels in vitreous of affected patients, together with the observation that myoFBs express both trkANGFR and p75NTR, suggests that NGF may be involved in ERMs.
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