Diabetic Macular Edema: Current Understanding, Molecular Mechanisms and Therapeutic Implications

Abstract

Diabetic retinopathy (DR), with increasing incidence, is the major cause of vision loss and blindness worldwide in working-age adults. Diabetic macular edema (DME) remains the main cause of vision impairment in diabetic patients, with its pathogenesis still not completely elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of DR and DME. Currently, intravitreal injection of anti-VEGF agents remains as the first-line therapy in DME treatment due to the superior anatomic and functional outcomes. However, some patients do not respond satisfactorily to anti-VEGF injections. More than 30% patients still exist with persistent DME even after regular intravitreal injection for at least 4 injections within 24 weeks, suggesting other pathogenic factors, beyond VEGF, might contribute to the pathogenesis of DME. Recent advances showed nearly all the retinal cells are involved in DR and DME, including breakdown of blood-retinal barrier (BRB), drainage dysfunction of Müller glia and retinal pigment epithelium (RPE), involvement of inflammation, oxidative stress, and neurodegeneration, all complicating the pathogenesis of DME. The profound understanding of the changes in proteomics and metabolomics helps improve the elucidation of the pathogenesis of DR and DME and leads to the identification of novel targets, biomarkers and potential therapeutic strategies for DME treatment. The present review aimed to summarize the current understanding of DME, the involved molecular mechanisms, and the changes in proteomics and metabolomics, thus to propose the potential therapeutic recommendations for personalized treatment of DME.

Flotillin-1 as a housekeeping target mediates Nrf2 inhibition of blood–retinal barrier ferroptosis in diabetic retinopathy

“…Disruption of the BRB is the primary cause of diabetic macular edema [6]. The RPE layer is made up of several highly differentiated monolayers of pigment epithelium that are arranged closely together [23][24][25].…”

Oral Chinese medicines for treating diabetic macular edema: Protocol for a systematic search of randomized studies and meta-analysis

“…Diabetic macular edema (DME) affects approximately 1 out of 15 adults with diabetes [1,2]. In accordance with the International Diabetes Federation, the number of adults living with diabetes is estimated to reach 783 million by 2045 [3]. The high incidence of DME seriously affects quality of life and puts a financial burden on healthcare systems.…”

Modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor for diabetic macular edema in Taiwan

“…DME is characterized by the alteration of blood-retina barrier, in which pericyte loss and vascular endothelial cell-cell junction breakdown result in leakage and accumulation of uid in the retina. The abnormalities of metabolic pathways induced by hyperglycemia lead to increased oxidative stress and in ammation, which in turn contribute to DME development [3,4] . Various cytokines and chemokines are involved in this pathogenesis, and elevated vascular endothelial growth factor (VEGF) is one of the potent contributors to vascular leakage and macula edema [5,6] .…”