Diabetic retinopathy: a complex pathophysiology requiring novel therapeutic strategies

Abstract

Introduction: Diabetic retinopathy (DR) is the leading cause of vision loss in the working age population of the developed world. DR encompasses a complex pathology, and one that is reflected in the variety of currently available treatments, which include laser photocoagulation, glucocorticoids, vitrectomy and agents which neutralize vascular endothelial growth factor (VEGF). Whilst these options demonstrate modest clinical benefits, none is yet to fully attenuate clinical progression or reverse damage to the retina.This has led to an interest in developing novel therapies for the condition, such as mediators of angiopoietin signaling axes, immunosuppressants, nonsteroidal anti-inflammatory drugs (NSAIDs), oxidative stress inhibitors and vitriol viscosity inhibitors. Further, preclinical research suggests that gene therapy treatment for DR could provide significant benefits over existing treatments options.Areas covered: Here we review the pathophysiology of DR and provide an overview of currently available treatments. We then outline recent advances made towards improved patient outcomes and highlight the potential of the gene therapy paradigm to revolutionize DR management.Expert opinion: Whilst significant progress has been made towards our understanding of DR, further research is required to enable the development of a detailed spatiotemporal model of the disease. In addition, we hope that improvements in our knowledge of the condition facilitate therapeutic innovations that continue to address unmet medical need and improve patient outcomes, with a focus on the development of targeted medicines.

Prospective exploratory study to assess the safety and efficacy of aflibercept in cystoid macular oedema associated with retinitis pigmentosa

“…In the case of diabetic retinopathy, raised circulating blood sugar is thought to cause dysregulation of several biochemical and molecular signalling pathways leading to the production of superoxide-free radicals and resultant oxidative stress in retinal tissues. 27 Mitochondrial dysfunction, inflammation, and hypoxia-driven VEGF release leads to vascular and neuronal apoptosis and neovascularisation and elevated vasopermeability, respectively. 27 …”

“… 27 Mitochondrial dysfunction, inflammation, and hypoxia-driven VEGF release leads to vascular and neuronal apoptosis and neovascularisation and elevated vasopermeability, respectively. 27 …”

MicroRNA-29b-3p Promotes Human Retinal Microvascular Endothelial Cell Apoptosis via Blocking SIRT1 in Diabetic Retinopathy

“…Once the blood-retina barrier is broken down, dangerous factors from the circulating blood will leak into the retinal tissue and cause irreversible damage to the retinal neural cells (Trost et al, 2016;Xu and Chen, 2017). Although a series of studies have been carried out to investigate the pathogenesis of human retinal vascular endothelial cell apoptosis (Santiago et al, 2018;Whitehead et al, 2018), the mechanism is largely unknown.…”

VEGF‐Trap is a potent modulator of vasoregenerative responses and protects dopaminergic amacrine network integrity in degenerative ischemic neovascular retinopathy

“…The identification of the vascular endothelial growth factor A (VEGF‐A) as a key player in hypoxia‐induced pathological angiogenesis (Shweiki et al ; Aiello ; Watkins et al ) boosted the development of anti‐VEGF‐A therapies against retinal neovascularization (Penn et al ; Kim and D'Amore ; Caplan and Kesselheim ; Miller ; Bolinger and Antonetti ; Whitehead et al ). Anti‐VEGF‐A agents reduce vascular leakiness, inhibit neovascularization, and improve visual acuity.…”