title: Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications.
abstract: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in developed countries, and its prevalence will increase as the global incidence of diabetes grows exponentially. DR begins with an early nonproliferative stage in which retinal blood vessels and neurons degenerate as a consequence of chronic hyperglycemia, resulting in vasoregression and persistent retinal ischemia, metabolic disequilibrium, and inflammation. This is conducive to overcompensatory pathological neovascularization associated with advanced proliferative DR. Although DR is considered a microvascular complication, the retinal microvasculature is intimately associated with and governed by neurons and glia; neurodegeneration, neuroinflammation, and dysregulation of neurovascular cross talk are responsible in part for vascular abnormalities in both early nonproliferative DR and advanced proliferative DR. Neuronal activity directly regulates microvascular dilation and blood flow in the process of neurovascular coupling. Retinal neurons also secrete guidance cues in response to injury, ischemia, or metabolic stress that may either promote or suppress vascular outgrowth, either alleviating or exacerbating DR, contingent on the stage of disease and retinal microenvironment. Neurodegeneration, impaired neurovascular coupling, and dysregulation of neuronal guidance cues are key events in the pathogenesis of DR, and correcting these events may prevent or delay development of advanced DR. The review discusses the mechanisms of neurovascular cross talk and its dysregulation in DR, and their potential therapeutic implications.
authors.affiliation: Depatment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Harold Hamm Diabetes Center, Oklahoma City, Oklahoma;
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Moran
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Zhongxiao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Departments of Ophthalmology, Biochemistry & Molecular Medicine, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Sapieha
authors.affiliation: Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; and.
authors.forename: Lois E H
authors.initials: LE
authors.lastname: Smith
authors.affiliation: Depatment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Harold Hamm Diabetes Center, Oklahoma City, Oklahoma; jian-xing-ma@ouhsc.edu.
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Ma
mesh_terms: D003930:Diabetic Retinopathy / Q000378:metabolism / Q000503:physiopathology*; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000502:physiology; D000069336:Neurovascular Coupling / Q000502:physiology*; D000072483:Placenta Growth Factor / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D055351:Retinal Neurons / Q000378:metabolism* / Q000502:physiology; D012171:Retinal Vessels / Q000378:metabolism / Q000503:physiopathology*; D039961:Semaphorins / Q000378:metabolism; D015843:Serpins / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000072483:Placenta Growth Factor; D010982:Platelet-Derived Growth Factor; D039961:Semaphorins; D015843:Serpins; D042442:Vascular Endothelial Growth Factors; D000099174:Pigment Epithelium-Derived Factor; C081848:NDP protein, human
keywords: angiogenesis; metabolism; retinal degeneration