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.

Keywords: CD146; angiogenesis; proliferative diabetic retinopathy; vascular endothelial growth factor receptor 2.