Molecular stress and neurovascular injury in the diabetic retina
Chuanyu Guo, Akrit Sodhi
Chuanyu Guo, Akrit Sodhi
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Molecular stress and neurovascular injury in the diabetic retina

Abstract

Diabetic retinopathy (DR), the most common microvascular complication in patients with diabetes mellitus (DM), is a leading cause of vision loss worldwide. Sustained hyperglycemia plays a central role in promoting DR. However, tight glycemic control does not prevent — and indeed sometimes worsens — DR, highlighting the importance of ongoing studies aimed at improving our understanding of this complex disease. Over the last few decades, the dogma that DR is a vascular disease that results in secondary neuronal injury has evolved, as emerging evidence suggests that neurodegeneration occurs in parallel with or prior to vascular cell injury in the retina of patients with DM. This has led to appreciation of DR as a neurovascular disease, characterized by microvascular injury and neurodegeneration, both of which contribute to vision loss. Here, we explore how molecular stress (i.e., glucose dysregulation, dysmetabolism, oxidative stress, and inflammation) promote retinal vascular cell and neuronal injury in patients with DM. We focus on how these processes influence, and are influenced by, genes regulated by the HIF family of transcription factors in glial, vascular, neuronal, and inflammatory cells, with the goal of identifying new therapeutic avenues for the prevention or early treatment of patients with this vision-threating disease.

Authors

Chuanyu Guo, Akrit Sodhi

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Figure 1

Retinal structure changes in diabetic retinopathy.

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Retinal structure changes in diabetic retinopathy. (A) Schematic diagram...
(A) Schematic diagram of the microvascular changes observed in NPDR. Intraretinal hemorrhages, microaneurysms, venous beading, and/or IRMA occur during the progression from early to moderate and severe NPDR. (B) Schematic diagram of PDR. Development of retinal NV occurs when newly formed abnormal blood vessels from the superficial vascular plexus (SVP) penetrate the ILM and enter the vitreous and develop into fibrovascular tissue. ICP, intermediate capillary plexus; DCP, deep capillary plexus. (C) Fluorescein angiogram from a patient with PDR. Inset shows fluorescein leakage from retinal neovascularization (red arrows). Areas of capillary drop out (nonperfused retina) are indicated by white asterisks. (D) Schematic diagram of DME. Breakdown of the iBRB results in the leakage of intravascular fluid and circulating lipids and proteins into the extravascular space of the neurosensory retina. (E) Spectral-domain optical coherence tomography from a patient with DME demonstrating loss of the foveal contour and the accumulation of intraretinal fluid (blue arrows) in the inner and outer retina. Patient images were obtained with informed consent from an IRB-approved clinical study at the Johns Hopkins University School of Medicine.