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

Autor:	Augustine J; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK., Pavlou S; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK., Harkin K; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK., Stitt AW; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK., Xu H; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK., Chen M; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2023 Sep 01; Vol. 16 (9). Date of Electronic Publication: 2023 Sep 06.
DOI:	10.1242/dmm.050174
Abstrakt:	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. Competing Interests: Competing interests S.P. is currently employed at AstraZeneca, UK. The remaining authors declare that they have no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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