Retinal fibrosis in diabetic retinopathy

Abstract

In response to injury, reparative processes are triggered to restore the damaged tissue; however, such processes are not always successful in rebuilding the original state. The formation of fibrous connective tissue is known as fibrosis, a hallmark of the reparative process. For fibrosis to be successful, delicately balanced cellular events involving cell proliferation, cell migration, and extracellular matrix (ECM) remodeling must occur in a highly orchestrated manner. While successful repair may result in a fibrous scar, this often restores structural stability and functionality to the injured tissue. However, depending on the functionality of the injured tissue, a fibrotic scar can have a devastating effect. For example, in the retina, fibrotic scarring may compromise vision and ultimately lead to blindness. In this review, we discuss some of the retinal fibrotic complications and highlight mechanisms underlying the development of retinal fibrosis in diabetic retinopathy.

Keywords: Diabetic retinopathy; Extracellular matrix; Müller cell; Retinal fibrosis; Vascular endothelial growth factor.

Figure 1

A schematic flowchart showing potential effects of diabetes or hyperglycemia on retinal fibrosis and vision loss in diabetic retinopathy. Diabetes and associated hyperglycemia can increase serum and vitreous levels of IGF-1, an angiogenic neuroprotective factor. IGF-1, hypoxia, and inflammation are all contributing factors, which can increase HIF-1α level. Upregulation of HIF-1α is known to contribute to Müller cell activation and induce angiogenic factors VEGF and bFGF that aid in the development and progression of neovascularization, which contributes to retinal fibrosis. The combined effect of new abnormal blood vessel growth and retinal fibrosis generates tractional forces, which pull on the retina, contributing to retinal detachment and subsequent vision loss, in diabetic retinopathy.

Figure 2

Diagram illustrating the development of retinal fibrosis in diabetic retinopathy and potential inhibitory strategies for prevention of proliferative fibrotic membranes associated with PDR.