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The mechanism by which choroidal pericytes are involved in the occurrence and development of subretinal fibrosis

Posting time:2022-12-02 06:30:43

The mechanism by which choroidal pericytes are involved in the occurrence and development of subretinal fibrosis

Editor's note: Age-related macular degeneration (AMD) is the leading cause of visual impairment and severe vision loss affecting older adults worldwide. In neovascular AMD, vascular endothelial growth factor (VEGF) plays a unique role in pathological angiogenesis and inflammation, and anti-VEGF therapy has become its first-line therapy, but neovascular AMD can develop subretinal fibrosis in advanced stages. It causes irreversible loss of vision, and there is currently no effective treatment and intervention measures for subretinal fibrosis, which is a difficult point in the treatment of neovascular AMD. Recently, Professor Zhang Jingfa from the Department of Ophthalmology of Shanghai First People's Hospital published an article entitled TGF-β promotes pericyte-myofibroblast transition in subretinal fibrosis through the Smad2/3 and Akt/mTOR pathways. This paper found that choroidal pericytes were involved in the occurrence and development of subretinal fibrosis and related mechanisms. The study was published in Experimental and Molecular Medicine (IF 12.153). In the mouse model of laser-induced choroidal neovascularization (CNV), the co-first authors Zhao Zhenzhen and Zhang Yumeng overexpressed TGF-β2 in the eye by intravitreal injection of rAAV2, and found that it significantly promoted the development of CNV in advanced lesions. Infiltration of cells and progression of subretinal fibrosis. TGF-β also plays an important role in the progression of wet AMD and subretinal fibrosis, and plays an important role in fibrosis by inducing proliferation, migration, activation and promotion of mesenchymal transition of multiple cell types. Pericytes are a type of cells embedded in the basement membrane of small blood vessels. In kidney, lung, and liver fibrosis, pericytes have been shown to be an important source of myofibroblasts and a key factor in fibrosis. In this study, by extracting and culturing primary choroidal pericytes, it was verified in vitro that TGF-β2 can significantly induce pericyte-myofibroblast transformation (PMT), cell proliferation and cell migration. Further study of the pathway mechanism revealed that knockdown of Smad2/3 or inhibition of Akt/mTOR could significantly attenuate PMT, inhibit proliferation and cell migration in perichoroidal cells. And the combined inhibition of Smad2/3 and mTOR has obvious synergistic effect on reducing the expression of α-SMA and cell proliferation. Finally, after intravitreal injection of an Akt/mTOR inhibitor in mice, an early multiple-dose regimen was found to significantly inhibit the proliferation of CNV late-stage pericytes and attenuate subretinal fibrosis. This study elucidates the effect of TGF-β2 on PMT in choroidal neovascularization and its possible mechanism leading to subretinal fibrosis. Targeting pericytes provides a potential new direction for the treatment of subretinal fibrosis. The author introduces Prof. Zhang Jingfa, Ph.D., Deputy Director of Shanghai Institute of Ophthalmology. Researcher, Deputy Chief Physician, Doctoral Supervisor, Postdoctoral Fellow of Harvard Medical School, Shanghai Pujiang Talent. Vice-chairman (and secretary) of Basic Research and Clinical Translation of the Fifth Committee of the Ophthalmologist Branch of the Chinese Medical Doctor Association, vice-chairman of the Youth Committee of the Ophthalmology Branch of the Chinese Geriatrics Association, member of the Standing Committee of the Precision Medicine Professional Committee of the Shanghai Biomedical Industry Association, etc. The clinical and scientific research direction is the pathogenesis and treatment of fundus diseases, focusing on diabetic retinopathy and age-related macular degeneration. Co-first author: Zhao Zhenzhen, a postgraduate student in the Department of Ophthalmology, First People's Hospital, Shanghai Jiaotong University School of Medicine Co-first author: Zhang Yumeng, a postgraduate student in the Department of Ophthalmology, the First People's Hospital, Shanghai Jiaotong University School of Medicine, search for "International Ophthalmology Newsletter" or "iophthal" to see more exciting content (source: "International Ophthalmology News" editorial department)

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