IL-33 regulates Müller cell-mediated retinal inflammation and neurodegeneration in diabetic retinopathy

Josy Augustine, Sofia Pavlou, Kevin Harkin, Alan W. Stitt, Heping Xu, Mei Chen*

*Corresponding author for this work

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Diabetic retinopathy (DR) is characterised by dysfunction of the retinal neurovascular unit, leading to visual impairment and blindness. Müller cells are key components of the retinal neurovascular unit and diabetes has a detrimental impact on these glial cells, triggering progressive neurovascular pathology of DR. Amongst many factors expressed by Müller cells, interleukin-33 (IL-33) has an established immunomodulatory role, and we investigated the role of endogenous IL-33 in DR. The expression of IL-33 in Müller cells increased during diabetes. Wild-type and Il33−/− mice developed equivalent levels of hyperglycaemia and weight loss following streptozotocin-induced diabetes. Electroretinogram a- and b-wave amplitudes, neuroretina thickness, and the numbers of cone photoreceptors and ganglion cells were significantly reduced in Il33−/− diabetic mice compared with those in wild-type counterparts. The Il33−/− diabetic retina also exhibited microglial activation, sustained gliosis, and upregulation of pro-inflammatory cytokines and neurotrophins. Primary Müller cells from Il33−/− mice expressed significantly lower levels of neurotransmitter-related genes (Glul and Slc1a3) and neurotrophin genes (Cntf, Lif, Igf1 and Ngf) under high-glucose conditions. Our results suggest that deletion of IL-33 promotes inflammation and neurodegeneration in DR, and that this cytokine is critical for regulation of glutamate metabolism, neurotransmitter recycling and neurotrophin secretion by Müller cells.

Original languageEnglish
Article numberdmm050174
Number of pages14
JournalDisease Models and Mechanisms
Issue number9
Publication statusPublished - Sep 2023


  • retina
  • interleukin-33
  • diabetic retinopathy
  • cytokines
  • neurotrophins
  • glial cells
  • neurovascular unit
  • Diabetes

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