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Franco Aparecido Rossato, Ashley Mackey, Yin Shan Eric Ng; The role of fibrosis and endothelial mesenchymal transition (EndoMT) in choroidal neovascularization (CNV) pathogenesis.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4077.
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© ARVO (1962-2015); The Authors (2016-present)
Investigate the role of fibrosis and EndoMT in CNV pathogenesis by determining the expression and localization of markers of fibrosis and EndoMT in an established mouse model of spontaneous CNV (sCNV).
The JR5558 sCNV mouse and age-matched wild-type mouse (C57BL/6J) were used as previously description (Nagai et. al., 2014). To determine the expression levels of different fibrosis and EndoMT markers in the sCNV lesions, immunohistochemisrty (IHC) analysis was performed on eye sections and whole mount of eyecups obtained from JR5558 and C57BL/6J animals at different time points to capture both, developing or established sCNV lesions. To determine if fibrosis is associated with sCNV, antibodies to alpha smooth muscle actin (αSMA) and collagen type III (Col-III) were used to localize their expression by IHC. To determine the potential association of EndoMT and inflammation with the sCNV, antibodies against Snail and P38 mitogen-activated protein kinases (p38 MAPK) were used in the IHC. FITC-conjugated isolection B4 (IB4) staining was used to identify sCNV in the eye samples.
Our staining data from eyecups with sCNV lesions from JR5558 mice indicated that αSMA-positive cells, likely myofibroblasts, are associated with sCNV and especially in more established sCNV lesions in older mice. Positive staining for Col-III as well as increased phosphorylation of p38 MAPK was detected surrounding the neovessels of the sCNV, which were identified by IB4 staining. Moreover, Snail expression was detected in the IB4-positive endothelial cells of the neovessels within the sCNV, as well as in myofibroblasts around the sCNV, suggesting a potential role of EndoMT in the pathogenesis of CNV in wet AMD.
Our results demonstrate that fibrosis and EndoMT are associated with the development of sCNV lesions observed in the JR5558 mouse. Furthermore, Snail expression was detected in the endothelial cells of the neovessels. Together, the data suggest a potential role of fibrosis and EndoMT during CNV pathogenesis.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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