1. Chronic social defeat stress causes retinal vascular dysfunction.
- Author
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Wang M, Milic M, Gericke A, Mercieca K, Liu H, Ruan Y, Jiang S, van Beers T, von Pein HD, Müller MB, and Prokosch V
- Subjects
- Actins metabolism, Adrenal Hyperplasia, Congenital physiopathology, Animals, Cell Survival, Chronic Disease, Corticosterone blood, Disease Models, Animal, Disorder of Sex Development, 46,XY physiopathology, Endothelin-1 metabolism, Intraocular Pressure physiology, Male, Mice, Mice, Inbred C57BL, Ocular Hypertension physiopathology, Optic Nerve physiopathology, Retinal Artery metabolism, Retinal Diseases metabolism, Retinal Ganglion Cells metabolism, Stress, Psychological metabolism, Tonometry, Ocular, Transcription Factor Brn-3A metabolism, Video Recording, Retinal Artery physiopathology, Retinal Diseases physiopathology, Retinal Ganglion Cells pathology, Social Defeat, Stress, Psychological physiopathology
- Abstract
Purpose: The roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss., Methods: Twelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only. Intraocular pressure (IOP) was measured with a rebound tonometer. Blood plasma corticosterone concentration and adrenal gland weight were used to assess stress levels. Brn-3a staining in retinas and PPD staining in optic nerve cross sections were conducted to assess the survival of RGCs and axons respectively. The ET-1 and α-SMA levels were determined in retina. Retinal vascular autoregulation, functional response to various vasoactive agents and vascular mechanics were measured using video microscopy., Results: No significant difference in IOP levels was observed during and after CSD between CSD mice and controls. CSD stress caused hypercortisolemia 2 days post-CSD. However, increased corticosterone levels went back to normal 8 months after CSD. CSD-exposed mice developed adrenal hyperplasia 3 days post-CSD, which was normalized by 8 months. RGC and axon survival were similar between CSD mice and controls. However, CSD stress caused irreversible, impaired autoregulation and vascular dysfunction of retinal arterioles in CSD mice. In addition, impaired maximal dilator capacity of retinal arterioles was observed 8 months post-CSD rather than 3 days post-CSD. Remarkably, ET-1 levels were increased 3 days post-CSD while α-SMA levels were decreased 8 months post-CSD., Conclusions: We found that CSD stress does not cause IOP elevation, nor loss of RGCs and their axons. However, it strikingly causes irreversible impaired autoregulation and endothelial function in murine retinal arterioles. In addition, CSD changed vascular mechanics on a long-term basis. Increased ET-1 levels and loss of pericytes in retina vessels may involve in this process., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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