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

Autor:	Fu Z; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Wang Z; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Liu CH; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Gong Y; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Cakir B; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Liegl R; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Sun Y; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Meng SS; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Burnim SB; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Arellano I; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Moran E; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Duran R; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Poblete A; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Cho SS; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Talukdar S; Merck Research Laboratories, Boston, MA., Akula JD; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA., Hellström A; Section for Ophthalmology, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden., Smith LEH; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA lois.smith@childrens.harvard.edu.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2018 May; Vol. 67 (5), pp. 974-985. Date of Electronic Publication: 2018 Feb 27.
DOI:	10.2337/db17-0830
Abstrakt:	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. PF-05231023 administration did not change retinal expression of vascular endothelial growth factor A, suggesting a novel therapeutic approach for the prevention of early diabetic retinopathy by protecting photoreceptor function in diabetes. (© 2018 by the American Diabetes Association.)
Databáze:	MEDLINE
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