Neurovascular regulation in diabetic retinopathy and emerging therapies

Liyang Ji, Hong Tian, Keith A Webster, Wei Li

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)5977-5985
Number of pages9
JournalCellular and Molecular Life Sciences
Issue number16
StatePublished - Aug 2021
Externally publishedYes


  • Diabetic retinopathy
  • Ligandomics
  • Neurovascular crosstalk
  • Neurovascular unit
  • Scg3
  • VEGF

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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