Transplantation of Bone Marrow Mesenchymal Stem Cells (BMSCs) Overexpressing Circular Zinc Finger Protein 609 Alleviates Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is a chronic complications and its pathogenesis remains unclear. This study aims to elucidate the underlying mechanism by how bone marrow mesenchymal stem cells (BMSCs) affects DR development in a rat model. A rat model of DR was established and injected with BMSCs overexpressing Cir-ZNF609 and shRNA Cir-ZNF609 to vitreous body followed by analysis of the retinal vascular permeability and macular retinal layers thickness, and the levels of HIF-1α, ICAM-1 and VEGF in rat retina by ELISA and immunohistochemistry. Injection of BMSCs overexpressing Cir-ZNF609 resulted in decreased HIF-1α ICAM-1 and VEGF expression, amelioration of retinal ganglion choriocapillaris injury and reducing ganglion cells. Twelve weeks after treatment, neovascularization took place and fibroblasts appeared with some nucleus disappearing and pigment taking off. Besides, permeability also elevated in the presence of overexpressing Cir-ZNF609 and penetration rate for Evans blue (16.36+3.25, 15.45±3.46 μg/g) was lower than healthy rats (28.66±2.08, 32.24±4.36 μg/g) and controls (26.93±3.03, 33.49±5.02 μg/g) (p < 0.01). Moreover, upregulation of Cir-ZNF609 decreased retinal thickness and macular volume in DR rats (p < 0.05). In conclusion, intravitreal injection of mouse BMSCs overexpressing Cir-ZNF609 alleviates retinal injury and decreases retinal thickness and macular volume, and enhances neovascularization. These evidence provides a novel insight into gene therapy for DR.