High Glucose and Glucose Deprivation Modulate Müller Cell Viability and VEGF Secretion

Abstract

IntroductionDiabetic retinopathy (DR) is a complication of the eye due to prolonged diabetes. In the United States, the prevalence of DR in a diabetic age group of 18 or older is 1 in 300 [1]. Glycemic control, diabetic duration, blood pressure control, blood lipids, among others are major determinants in the development and severity of DR [2][3][4][5]. Nonproliferative diabetic retinopathy (NPDR) is characterized by loss of capillaries, pericyte dropout, and formation of microaneurysms [6][7][8][9]. NPDR progression to proliferative stage (PDR) is characterized by neovascularization and excessive angiogenesis [10][11][12] which causes swelling of capillaries and leakage of fluids on aqueous and vitreous humors, as well as retinal detachment [13], eventually leading to partial or complete vision loss.There are various growth factors associated with diabetic retinopathy [14]. One of the widely investigated known growth factors is Vascular Endothelial Growth Factor (VEGF). VEGF is a group of glycoproteins existing in many isoforms [15]. VEGF/VEGF-A (a 45KDa glycoprotein) is known to promote neovascularization and angiogenesis [16,17]. VEGF is secreted by retinal pigment epithelial cells, endothelial cells, pericytes, ganglion cells, choroidal fibroblast cells, Müller cells and others in the retina [18][19][20][21][22][23][24]. The VEGF levels in DR may partly be elevated due to oxidative stress, glycation products [25], and hypoxia.Müller cells are one of the three types of glial cells in the retina. They span radially along the thickness of the retina and play a

Unfolded Protein Response Pathways Correlatively Modulate Endoplasmic Reticulum Stress Responses in Rat Retinal Müller Cells

“…However, how ERS in rMCs under HG promotes VEGF expression remains poorly understood. Previous studies showed that Müller cells are capable of basal VEGF secretion and of VEGF synthesis in HG [23, 28, 29].…”