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Current understanding of the molecular and cellular pathology of diabetic retinopathy


Diabetes mellitus has profound effects on multiple organ systems; however, the loss of vision caused by diabetic retinopathy might be one of the most impactful in a patient’s life. The retina is a highly metabolically active tissue that requires a complex interaction of cells, spanning light sensing photoreceptors to neurons that transfer the electrochemical signal to the brain with support by glia and vascular tissue. Neuronal function depends on a complex inter-dependency of retinal cells that includes the formation of a blood–retinal barrier. This dynamic system is negatively affected by diabetes mellitus, which alters normal cell–cell interactions and leads to profound vascular abnormalities, loss of the blood–retinal barrier and impaired neuronal function. Understanding the normal cell signalling interactions and how they are altered by diabetes mellitus has already led to novel therapies that have improved visual outcomes in many patients. Research highlighted in this Review has led to a new understanding of retinal pathophysiology during diabetes mellitus and has uncovered potential new therapeutic avenues to treat this debilitating disease.

Key points

  • Diabetic retinopathy is a leading cause of blindness that disrupts the normal interaction of the retinal neural and vascular components leading to vascular permeability, neovascularization and loss of proper neural function.

  • Current effective therapeutic approaches target vascular endothelial growth factor, while a host of new therapies targeting vascular endothelial and pericyte signalling and inflammatory cytokines are being tested for diabetic retinopathy.

  • Stem cell therapy for vascular regeneration holds potential for restorative therapeutic approaches in diabetic retinopathy.

  • Understanding the neuronal and glial changes that drive loss of vision is rapidly emerging, and targeted approaches to directly test the relationship between the neurovascular unit and alteration in diabetic retinopathy are needed.

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Fig. 1: Diabetic retinopathy manifests with multiple pathologies.
Fig. 2: The neurovascular unit and cytokine signalling in diabetic retinopathy.


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Correspondence to David A. Antonetti.

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The clear gel filling the space between the retina and the lens.


The vascular bed adjacent to the retinal pigmented epithelium (RPE) supporting the rods and cones of the outer retina that are on the opposing side of the RPE.

Posterior pole

The posterior segment of the human retina visible during ophthalmoscopy made up of the optic disc (optic nerve head) and macula, or avascular central area including the fovea, or thinned retina with high cone density responsible for high visual acuity.

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Antonetti, D.A., Silva, P.S. & Stitt, A.W. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat Rev Endocrinol 17, 195–206 (2021).

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