Diabetic Müller-Glial-Cell-Specific Il6ra Knockout Mice Exhibit Accelerated Retinal Functional Decline and Thinning of the Inner Nuclear Layer.

Autor:	Glass J; Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia, United States., Robinson RL; Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia, United States., Greenway G; Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia, United States., Jones G; Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia, United States., Sharma S; Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia, United States.; Culver Vision Discovery Institute, Augusta University, Augusta, Georgia, United States.; Department of Ophthalmology, Augusta University, Augusta, Georgia, United States.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2023 Dec 01; Vol. 64 (15), pp. 1.
DOI:	10.1167/iovs.64.15.1
Abstrakt:	Purpose: Interleukin-6 (IL-6) is implicated in the pathology of diabetic retinopathy (DR). IL-6 trans-signaling via soluble IL-6 receptor (IL-6R) is primarily responsible for its pro-inflammatory functions, whereas cis-signaling via membrane-bound IL-6R is anti-inflammatory. Using a Müller-glial-cell-specific Il6ra-/- mouse, we examined how loss of IL-6 cis-signaling in Müller glial cells (MGCs) affected retinal thinning and electroretinography (ERG) response over 9 months of diabetes. Methods: Diabetes was induced in wildtype and knockout mice with streptozotocin (40 mg/kg, daily for 5 days). Spectral domain optical coherence tomography (SD-OCT), ERG, and fundoscopy/fluorescein angiography (FA) were assessed at 2, 6, and 9 months of diabetes. MGCs and bipolar neurons were examined in retinal tissue sections by immunofluorescence. Results: Diabetic MGC Il6ra-/- mice had significantly thinner retinas than diabetic wildtype mice at 2 (-7.6 µm), 6 (-12.0 µm), and 9 months (-5.0 µm) of diabetes, as well as significant thinning of the inner nuclear layer (INL). Diabetic MGC Il6ra-/- mice also showed a reduction in scotopic B-wave amplitude and B-wave/A-wave ratio earlier than wildtype diabetic mice. In retinal sections, we found a decrease in bipolar neuronal marker PKCα only in diabetic MGC Il6ra-/- mice, which was significantly lower than both controls and diabetic wildtype mice. Glutamine synthetase, a Müller cell marker, was reduced in both wildtype and MGC Il6ra-/- diabetic mice compared to their respective controls. Conclusions: IL-6 cis-signaling in MGCs contributes to maintenance of the INL in diabetes, and loss of the IL-6 receptor reduces MGC-mediated neuroprotection of bipolar neurons in the diabetic retina.
Databáze:	MEDLINE
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