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Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications.
Am J Physiol Heart Circ Physiol. 2016 09 01; 311(3):H738-49.AJ

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+Show Affiliations

Depatment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Harold Hamm Diabetes Center, Oklahoma City, Oklahoma;Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; and.Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; and.Departments of Ophthalmology, Biochemistry & Molecular Medicine, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; and.Depatment of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Harold Hamm Diabetes Center, Oklahoma City, Oklahoma; jian-xing-ma@ouhsc.edu.

Pub Type(s)

Journal Article
Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27473938

Citation

Moran, Elizabeth P., et al. "Neurovascular Cross Talk in Diabetic Retinopathy: Pathophysiological Roles and Therapeutic Implications." American Journal of Physiology. Heart and Circulatory Physiology, vol. 311, no. 3, 2016, pp. H738-49.
Moran EP, Wang Z, Chen J, et al. Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications. Am J Physiol Heart Circ Physiol. 2016;311(3):H738-49.
Moran, E. P., Wang, Z., Chen, J., Sapieha, P., Smith, L. E., & Ma, J. X. (2016). Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications. American Journal of Physiology. Heart and Circulatory Physiology, 311(3), H738-49. https://doi.org/10.1152/ajpheart.00005.2016
Moran EP, et al. Neurovascular Cross Talk in Diabetic Retinopathy: Pathophysiological Roles and Therapeutic Implications. Am J Physiol Heart Circ Physiol. 2016 09 1;311(3):H738-49. PubMed PMID: 27473938.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications. AU - Moran,Elizabeth P, AU - Wang,Zhongxiao, AU - Chen,Jing, AU - Sapieha,Przemyslaw, AU - Smith,Lois E H, AU - Ma,Jian-Xing, Y1 - 2016/07/29/ PY - 2016/01/06/received PY - 2016/07/18/accepted PY - 2016/7/31/entrez PY - 2016/7/31/pubmed PY - 2017/6/27/medline KW - angiogenesis KW - metabolism KW - retinal degeneration SP - H738 EP - 49 JF - American journal of physiology. Heart and circulatory physiology JO - Am J Physiol Heart Circ Physiol VL - 311 IS - 3 N2 - 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. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/27473938/Neurovascular_cross_talk_in_diabetic_retinopathy:_Pathophysiological_roles_and_therapeutic_implications_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.00005.2016?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -