The pathogenesis of diabetic retinopathy: old concepts and new questions

Abstract

Hyperglycaemia appears to be a critical factor in the aetiology of diabetic retinopathy and initiates downstream events including: basement membrane thickening, pericyte drop out and retinal capillary non-perfusion. More recently, focus has been directed to the molecular basis of the disease process in diabetic retinopathy. Of particular importance in the development and progression of diabetic retinopathy is the role of growth factors (eg vascular endothelial growth factor, placenta growth factor and pigment epithelium-derived factor) together with specific receptors and obligate components of the signal transduction pathway needed to support them. Despite these advances there are still a number of important questions that remain to be answered before we can confidently target pathological signals. How does hyperglycaemia regulate retinal vessels? Which growth factors are most important and at what stage of retinopathy do they operate? What is the preferred point in the growth factor signalling cascade for therapeutic intervention? Answers to these questions will provide the basis for new therapeutic interventions in a debilitating ocular condition.

Diabetes changes ionotropic glutamate receptor subunit expression level in the human retina

“…The vascular changes that occur in DR are well documented, and include loss of pericytes and endothelial cells, the formation of microaneurysms, basement membrane thickening and blood-retinal barrier breakdown (Cai and Boulton, 2002). In addition to the vascular …”

Risk evaluation of outcome of vitreous surgery based on vitreous levels of cytokines

“…All three fundus parameters (NVE, NVD, and FPE) reflect retinal neovascularization, while VEGF and IL-6 are involved in the onset and progression of new vessel formation. 1,2,9 It was suggested that the additional laser was needed to reduce the activity of new vessel formation during surgery in the advanced cases. Therefore, active neovascularization is associated with the progression of PDR.…”

“…1 Activity of PDR and outcome of vitreous surgery may be associated with several factors, but are inconclusive. Numerous cytokines and growth factors have been implicated in the pathogenesis and progression of PDR.…”

“…Numerous cytokines and growth factors have been implicated in the pathogenesis and progression of PDR. 1 Vascular endothelial growth factor (VEGF) is an angiogenic and permeabilityenhancing glycoprotein that predominantly acts on endothelial cells, and VEGF has been shown to increase in patients with active intraocular neovascularization. [1][2][3] Recently, it has been suggested that chronic subclinical inflammation may underlie much of the vascular pathology of diabetic retinopathy.…”

“…1 Vascular endothelial growth factor (VEGF) is an angiogenic and permeabilityenhancing glycoprotein that predominantly acts on endothelial cells, and VEGF has been shown to increase in patients with active intraocular neovascularization. [1][2][3] Recently, it has been suggested that chronic subclinical inflammation may underlie much of the vascular pathology of diabetic retinopathy. 4 Interleukin-6 (IL-6) is a multifunctional cytokine 5 that may be a major mediator of anterior uveitis 6 and proliferative vitreoretinopathy (PVR).…”