2026/03/01 by Chuanyu Guo, Akrit Sodhi · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Connexins and lens biology #Endoplasmic Reticulum Stress and Disease #Retinal Diseases and Treatments
paper · doi:10.1172/jci200945
openalex created_date 2026/03/01 · openalex publication_date 2026/03/01 · openalex updated_date 2026/07/12
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.