title: Müller Glia Are a Major Cellular Source of Survival Signals for Retinal Neurons in Diabetes.
abstract: To dissect the role of vascular endothelial growth factor receptor-2 (VEGFR2) in Müller cells and its effect on neuroprotection in diabetic retinopathy (DR), we disrupted VEGFR2 in mouse Müller glia and determined its effect on Müller cell survival, neuronal integrity, and trophic factor production in diabetic retinas. Diabetes was induced with streptozotocin. Retinal function was measured with electroretinography. Müller cell and neuronal densities were assessed with morphometric and immunohistochemical analyses. Loss of VEGFR2 caused a gradual reduction in Müller glial density, which reached to a significant level 10 months after the onset of diabetes. This observation was accompanied by an age-dependent decrease of scotopic and photopic electroretinography amplitudes and accelerated loss of rod and cone photoreceptors, ganglion cell layer cells, and inner nuclear layer neurons and by a significant reduction of retinal glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. Our results suggest that VEGFR2-mediated Müller cell survival is required for the viability of retinal neurons in diabetes. The genetically altered mice established in this study can be used as a diabetic animal model of nontoxin-induced Müller cell ablation, which will be useful for exploring the cellular mechanisms of neuronal alteration in DR.
authors.affiliation: Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, China Section of Endocrinology and Diabetes, Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Fu
authors.affiliation: Section of Endocrinology and Diabetes, Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Shuqian
authors.initials: S
authors.lastname: Dong
authors.affiliation: Section of Endocrinology and Diabetes, Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Meili
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: David M
authors.initials: DM
authors.lastname: Sherry
authors.affiliation: Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Changyun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: You
authors.affiliation: Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent, Belgium Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University and Alfred Health Centre, Melbourne, Victoria, Australia Department of Clinical Haematology, Monash University and Alfred Health Centre, Melbourne, Victoria, Australia.
authors.forename: Jody J
authors.initials: JJ
authors.lastname: Haigh
authors.affiliation: Section of Endocrinology and Diabetes, Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK Department of Ophthalmology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK Harold Hamm Diabetes Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK yun-le@ouhsc.edu.
authors.forename: Yun-Zheng
authors.initials: YZ
authors.lastname: Le
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000473:pathology*; D004596:Electroretinography; D063928:Ependymoglial Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D055351:Retinal Neurons / Q000502:physiology*; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2