Diabetic Retinopathy: Pathophysiology and New Pathways

Abstract

Nakhoul F. Nakhoul and Darawsha Mamdoh

Diabetic retinopathy is one of the most common microvascular complications of diabetes mellitus, which is associated with damage of blood-retinal barrier and ischemia of retinal vasculature. Consequently, there is a decrease in visual acuity due to leakage of retinal vessels and aberrant pathological angiogenesis. Different studies have shown that autophagy & klotho proteins can plays an important role in the pathogenesis of DR,

Type 2 diabetes mellitus, is associated with increased glucose cell toxicity and oxidative stress that can lead to irreversible damage in retina. Autophagy plays a critical role in degradation of damaged intracellular proteins to maintain intracellular homeostasis. The Klotho is a circulating anti-aging hormone with anti-oxidative and anti-inflammatory properties with vascular protective effects. The disturbance of autophagy and klotho pathways are involved in the pathogenesis of diabetic retinopathy, especially the expression of klotho, ATG5 and its collaborator LC3-II. In early stages of diabetic retinopathy, klotho protein expression decreased, and LC3-II/ ATG5 proteins levels are increased.

Laser therapy, anti-VEGF intra-ocular injection, and vitrectomy are the conventional treatments in proliferative retinopathy but their capacity to reverse visual impairment are poor. Recently, different investigators showed that, the new anti-diabetic drugs such as the sodium-glucose transporter 2 inhibitors and the GLP-1 receptor agonists could be protective in early stages of diabetic retinopathy. In this review, we will present the suggested recent new pathways involved in early diabetic retinopathy and the recent anti-diabetic drugs such as the sodium-glucose transporter 2 inhibitors and the GLP-1 receptor agonist used in patients with type 2 diabetes mellitus that can be protective drugs against the progression of diabetic retinopathy.

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