@article {1302163, title = {Fibroblast Growth Factor 21 Protects Photoreceptor Function in Type 1 Diabetic Mice}, journal = {Diabetes}, volume = {67}, number = {5}, year = {2018}, month = {2018 05}, pages = {974-985}, 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. 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.}, keywords = {Animals, Antibodies, Monoclonal, Humanized, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Diabetic Retinopathy, Disease Models, Animal, Electroretinography, Fibroblast Growth Factors, Interleukin-1beta, Male, Mice, NF-E2-Related Factor 2, Photoreceptor Cells, Vertebrate, Proto-Oncogene Proteins c-akt, Retinal Neurons, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A}, issn = {1939-327X}, doi = {10.2337/db17-0830}, author = {Fu, Zhongjie and Wang, Zhongxiao and Liu, Chi-Hsiu and Gong, Yan and Cakir, Bertan and Liegl, Raffael and Sun, Ye and Meng, Steven S and Burnim, Samuel B and Arellano, Ivana and Moran, Elizabeth and Duran, Rubi and Poblete, Alexander and Cho, Steve S and Talukdar, Saswata and Akula, James D and Hellstr{\"o}m, Ann and Smith, Lois E H} }