Fibroblast Growth Factor 21 Protects Photoreceptor Function in Type 1 Diabetic Mice

Diabetes
Zhongjie FuLois Eh Smith

Abstract

Retinal neuronal abnormalities occur before vascular changes in diabetic retinopathy. Accumulating experimental evidence suggests that neurons control vascular pathology in diabetic and other neovascular retinal diseases. Therefore, normalizing neuronal activity in diabetes may prevent vascular pathology. We investigated whether fibroblast growth factor 21 (FGF21) prevented retinal neuronal dysfunction in insulin-deficient diabetic mice. We found that in diabetic neural retina, photoreceptor rather than inner retinal function was most affected and administration of the long-acting FGF21 analog PF-05231023 restored the retinal neuronal functional deficits detected by electroretinography. PF-05231023 administration protected against diabetes-induced disorganization of photoreceptor segments seen in retinal cross section with immunohistochemistry and attenuated the reduction in the thickness of photoreceptor segments measured by optical coherence tomography. PF-05231023, independent of its downstream metabolic modulator adiponectin, reduced inflammatory marker interleukin-1β (IL-1β) mRNA levels. PF-05231023 activated the AKT-nuclear factor erythroid 2-related factor 2 pathway and reduced IL-1β expression in stressed photoreceptors...Continue Reading

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Citations

Sep 6, 2019·EMBO Molecular Medicine·Zhongjie FuLois Eh Smith
Jun 6, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Huan LiuLi Lin
Feb 27, 2020·International Journal of Molecular Sciences·Zhongjie FuLois E H Smith
Feb 15, 2020·International Journal of Molecular Sciences·Yohei TomitaLois E H Smith
Feb 9, 2020·Journal of Clinical Medicine·Esraa ShoshaRuth B Caldwell
Mar 27, 2020·Frontiers in Pharmacology·Tianxi WangYe Sun
Sep 3, 2020·International Journal of Molecular Sciences·Yohei TomitaToshihide Kurihara
Aug 3, 2019·Endocrine·Simone Rosell RaskMette Bjerre
Nov 28, 2019·International Journal of Molecular Sciences·Yohei TomitaToshihide Kurihara
Oct 23, 2020·Biomedicines·Yohei TomitaToshihide Kurihara
Nov 15, 2020·Progress in Retinal and Eye Research·Deoye Tonade, Timothy S Kern
Nov 21, 2021·Experimental & Molecular Medicine·Yohei TomitaZhongjie Fu
Jan 18, 2022·European Journal of Ophthalmology·Nur Yasmin Diana Binti Lokman HakimSoon-Keng Cheong

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