2. Academic Validation
  3. Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy

Angiogenic and Fibrogenic Dual-effect of Gremlin1 on Proliferative Diabetic Retinopathy

  • Int J Biol Sci. 2024 Jan 12;20(3):897-915. doi: 10.7150/ijbs.85735.
Xinjing Wu 1,  Bing Qin 2,  Ruiwen Cheng 1,  Ru Zhou 1 3,  Xingxing Wang 1,  Zhengyu Zhang 1,  Xiying Mao 1,  Zhan Xie 1,  Mingkang Chen 1,  Lin Jiang 4,  Ping Xie 1,  Jiangdong Ji 1,  Weiwei Zhang 1,  Songtao Yuan 1,  Zizhong Hu 1,  Qinghuai Liu 1
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • 2 Department of Ophthalmology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian 223800, China.
  • 3 Department of Ophthalmology, People's Hospital of Yangzhong City, Yangzhong 212200, China.
  • 4 Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
PMID: 38250154 DOI: 10.7150/ijbs.85735
Abstract

Ocular angiogenic diseases, such as proliferative diabetic retinopathy (PDR), are often characterized by pathological new vessels and fibrosis formation. Anti-vascular endothelial growth factor (VEGF) therapy, despite of its efficiency to inhibit new vessels, has limitations, including drug resistance and retinal fibrosis. Here, we identified that Gremlin1, a novel angiogenesis and fibrosis inducer, was secreted from Müller glial cells, and its expression increased in the vitreous fluid from patients with PDR. Mechanistically, Gremlin1 triggered angiogenesis by promoting endothelial-mesenchymal transition via the EGFR/RhoA/ROCK pathway. In addition, Gremlin1 activated microglia to present profibrotic and fibrogenic properties. Further, anti-Gremlin1 antibody inhibited ocular angiogenesis and microglia fibrosis in mouse models. Collectively, Gremlin1 could be a potential therapeutic target in the treatment of ocular angiogenic diseases.

Keywords

Angiogenesis; Fibrosis; Gremlin1; Microglia; Proliferative diabetic retinopathy.

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