The Eyes Absent Proteins in Developmental and Pathological Angiogenesis

The American Journal of Pathology
Yuhua WangRashmi S Hegde

Abstract

Management of neoangiogenesis remains a high-value therapeutic goal. A recently uncovered association between the DNA damage repair pathway and pathological angiogenesis could open previously unexplored possibilities for intervention. An attractive and novel target is the Eyes absent (EYA) tyrosine phosphatase, which plays a critical role in the repair versus apoptosis decision after DNA damage. This study examines the role of EYA in the postnatal development of the retinal vasculature and under conditions of ischemia-reperfusion encountered in proliferative retinopathies. We find that the ability of the EYA proteins to promote endothelial cell (EC) migration contributes to a delay in postnatal development of the retinal vasculature when Eya3 is deleted specifically in ECs. By using genetic and chemical biology tools, we show that EYA contributes to pathological angiogenesis in a model of oxygen-induced retinopathy. Both in vivo and in vitro, loss of EYA tyrosine phosphatase activity leads to defective assembly of γ-H2AX foci and thus to DNA damage repair in ECs under oxidative stress. These data reveal the potential utility of EYA tyrosine phosphatase inhibitors as therapeutic agents in inhibiting pathological neovascularizati...Continue Reading

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Citations

May 20, 2017·BMC Cancer·Stephen RiffleRashmi S Hegde
Aug 5, 2017·Journal of Experimental & Clinical Cancer Research : CR·Stephen Riffle, Rashmi S Hegde
Jul 31, 2020·Critical Reviews in Biochemistry and Molecular Biology·Rashmi S HegdeRam Naresh Pandey
Jan 22, 2021·Human Genetics·Angèle Tingaud-SequeiraCaroline Rooryck
Sep 10, 2017·The International Journal of Biochemistry & Cell Biology·Hengbo ZhouRui Zhao
May 1, 2021·International Journal of Molecular Sciences·Kaushik Roychoudhury, Rashmi S Hegde
Jul 2, 2021·Biochemical Society Transactions·Upendra Kumar SoniRashmi S Hegde

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