Neurovascular Regulation in Diabetic Retinopathy and Emerging Therapies

Authors

Liyang Ji
Hong Tian
Keith A Webster
Wei Li

Publication Date

8-1-2021

Journal

Cellular and Molecular Life Sciences

DOI

10.1007/s00018-021-03893-9

PMID

34230991

PMCID

PMC8602033

PubMedCentral® Posted Date

7-7-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Chromogranins, Diabetes Mellitus, Diabetic Retinopathy, Humans, Neovascularization, Pathologic, Neurons, Retina, Retinal Vessels, Signal Transduction, Vascular Endothelial Growth Factor A, Neurovascular unit, Neurovascular crosstalk, VEGF, Scg3, Ligandomics

Abstract

Diabetic retinopathy (DR) is the leading cause of vision loss in working adults in developed countries. The disease traditionally classified as a microvascular complication of diabetes is now widely recognized as a neurovascular disorder resulting from disruption of the retinal neurovascular unit (NVU). The NVU comprising retinal neurons, glia and vascular cells coordinately regulates blood flow, vascular density and permeability to maintain homeostasis. Disturbance of the NVU during DR can lead to vision-threatening clinical manifestations. A limited number of signaling pathways have been identified for intercellular communication within the NVU, including vascular endothelial growth factor (VEGF), the master switch for angiogenesis. VEGF inhibitors are now widely used to treat DR, but their limited efficacy implies that other signaling molecules are involved in the pathogenesis of DR. By applying a novel screening technology called comparative ligandomics, we recently discovered secretogranin III (Scg3) as a unique DR-selective angiogenic and vascular leakage factor with therapeutic potential for DR. This review proposes neuron-derived Scg3 as the first diabetes-selective neurovascular regulator and discusses important features of Scg3 inhibition for next-generation disease-targeted anti-angiogenic therapies of DR.

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