2. Academic Validation
  3. ADAMTS5 promotes neovascularization via autophagic degradation of PEDF in proliferative diabetic retinopathy

ADAMTS5 promotes neovascularization via autophagic degradation of PEDF in proliferative diabetic retinopathy

  • Exp Eye Res. 2023 Jul 23;234:109597. doi: 10.1016/j.exer.2023.109597.
Zhao Geng 1,  Jun Tan 1,  Jie Xu 1,  Qifang Chen 1,  Peilin Gu 1,  Xiaoyan Dai 2,  Xunjie Kuang 2,  Shuxing Ji 1,  Ting Liu 3,  Chongyi Li 4
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Daping Hospital, Army Medical University, Chongqing, China.
  • 2 Cancer Center, Daping Hospital, Army Medical University, Chongqing, China.
  • 3 Department of Ophthalmology, Daping Hospital, Army Medical University, Chongqing, China. Electronic address: tingliu1597@126.com.
  • 4 Department of Ophthalmology, Daping Hospital, Army Medical University, Chongqing, China. Electronic address: lichongyi@tmmu.edu.cn.
PMID: 37490993 DOI: 10.1016/j.exer.2023.109597
Abstract

Proliferative diabetic retinopathy (PDR) adversely affects visual function. Extracellular matrix proteins (ECM) contribute significantly to the development of PDR. A Disintegrin and Metalloproteinase with Thrombospondin motifs 5 (ADAMTS5) is a member of ECM proteins. ADAMTS5 participates in angiogenesis and inflammation in diverse diseases. However, the role of ADAMTS5 in PDR remains elusive. Multiplex beam array technology was used to analyze vitreous humor of PDR patients and normal people. ELISA and Western blot were used to detect the expression of ADAMTS5, PEDF and Autophagy related factors. Immunofluorescence assay was used to mark the expression and localization of ADAMTS5 and PEDF. The neovascularization was detected by tube formation test. Our results revealed that ADAMTS5 expression was increased in the vitreous humor of PDR patients and oxygen-induced retinopathy (OIR) mice retinas. Inhibiting ADAMTS5 alleviated pathological angiogenesis and upregulated PEDF expression in the OIR mice. In addition, ADAMTS5 inhibited PEDF secretion in ARPE-19 cells in vitro studies, thereby inhibiting the migration of HMEC-1. Mechanically, ADAMTS5 promoted the autophagic degradation of PEDF. Collectively, inhibition of ADAMTS5 during OIR suppresses pathological angiogenesis. Our study provides a new approach for resolving pathological angiogenesis in PDR.

Keywords

ADAMTS5; Autophagy; PEDF; Pathological angiogenesis.

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