Abstract

Diabetic retinopathy (DR) is one of the most common causes of blindness globally. Proliferative DR (PDR), an advanced stage of DR, is characterized by the formation of fibrotic membranes at the vitreoretinal interface. The proliferation, migration, and secretion of extracellular matrix molecules in retinal pigment epithelial (RPE) cells contribute to the formation of fibrotic membranes in PDR. Gremlin has been reported to be upregulated in response to elevated glucose levels in the retina of diabetic rat and bovine pericytes. However, the role of gremlin in PDR remains unclear. In the present study, the vitreous concentrations of gremlin were significantly higher in the PDR (67.79 ± 33.96) group than in the control (45.31 ± 12.31) group, and high glucose levels induced the expression of gremlin in RPE cells. The elevated expression of extracellular matrix molecules, such as fibronectin and collagen IV, was significantly reduced by gremlin siRNA in human RPE cells under high-glucose conditions. Thus, gremlin may play a vital role in the development of PDR.

Highlights

  • Diabetic retinopathy (DR) is the major cause of adult blindness globally [1]

  • An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the concentration of gremlin in individuals with Proliferative DR (PDR) and in those with idiopathic epimacular membrane

  • The high levels of extracellular matrix molecules were detected in many organs of patients with diabetes mellitus and cell types under elevated glucose conditions [18,19,20,21]

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Summary

Introduction

Sustained high glucose levels play a vital role in the development of DR. Retinal pigment epithelial (RPE) cells, which lie between Bruch’s membrane and the retina, create the outer blood-retinal barrier (OBRB) and play a vital role in the pathological processes that lead to the vision loss. Gremlin is a secretory protein composed of highly conserved 184 amino acids [5,6,7,8]. This protein is a member of the structural cysteine knot superfamily and is present in both soluble and cell-associated forms [9,10,11,12]. Gremlin has been reported to be localised to the retina of diabetic rats, and the high levels of its expression have been demonstrated in bovine retinal pericytes under high-glucose conditions, compared with the control group [15]

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