Inhibition of CD146 attenuates retinal neovascularization via vascular endothelial growth factor receptor 2 signalling pathway in proliferative diabetic retinopathy

Abstract

Purpose To investigate the expression of CD146 and its role in proliferative diabetic retinopathy (PDR). Methods Enzyme linked immunosorbent assay was performed to analyse the expression and relationship of sCD146, vascular endothelial growth factor (VEGF), sVEGFR1 and sVEGFR2 in vitreous specimens from PDR and idiopathic epiretinal membranes (IERM) or idiopathic macular hole patients. The location of CD146 in ERMs was detected by immunofluorescence. The oxygen‐induced retinopathy (OIR) mice model was established and the adeno‐associated virus expressing a shRNA of CD146 (AAV1‐shCD146‐GFP) was administered via intravitreal injection. The effect of AAV1‐shCD146‐GFP was explored by immunofluorescence, Western blot and quantitative real‐time PCR. Results The levels of sCD146 in vitreous specimens from PDR patients and CD146 in retinas from OIR mice were significantly increased. Immunofluorescence showed that CD146 was co‐located with CD31, VEGF, VEGFR1 and VEGFR2, respectively. Intravitreal injection of AAV1‐shCD146‐GFP could dramatically reduce the formation of neovascularization and non‐perfusion area by inhibiting VEGFR2 phosphorylation. Conclusion Our results indicated that CD146 was involved in the development of retinal neovascularization via VEGFR2 pathway. Anti‐CD146 may be an innovative or adjuvant therapy, which provides a new direction for the treatment of PDR and other ocular neovascular diseases.

Immunohistochemical localization of CD146 and alpha‐smooth muscle actin during dentin formation and regeneration

“…Joshkon et al (2020) reported that CD146 and its soluble form play a major role in physiological and pathological angiogeneses. Moreover, CD146 is involved in angiogenesis as a co‐receptor for vascular endothelial growth factor receptor 2 (FLK1), which is involved in vascular endothelial cell development and proliferation (Jiang et al, 2012; Lin et al, 2022). Therefore, CD146 likely induces blood vessels in the area before dentin formation begins (Figure 7b).…”