Loss of Caveolin-1 Impairs Light Flicker-Induced Neurovascular Coupling at the Optic Nerve Head

Glaucoma is a neurodegenerative disease, which results in characteristic visual field defects. Intraocular pressure (IOP) remains the main risk factor for this leading cause of blindness. Recent studies suggest that disturbances in neurovascular coupling (NVC) may be associated with glaucoma. The re...

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Autores principales:	Jing Hong Loo, Ying Shi Lee, Chang Yi Woon, Victor H. K. Yong, Bingyao Tan, Leopold Schmetterer, Rachel S. Chong
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	glaucoma neurovascular coupling caveolin neuroprotection neurovascular dysfunction Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/ffd6621db4be44f3bb54166ce463c018
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spelling	oai:doaj.org-article:ffd6621db4be44f3bb54166ce463c0182021-11-08T06:34:34ZLoss of Caveolin-1 Impairs Light Flicker-Induced Neurovascular Coupling at the Optic Nerve Head1662-453X10.3389/fnins.2021.764898https://doaj.org/article/ffd6621db4be44f3bb54166ce463c0182021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.764898/fullhttps://doaj.org/toc/1662-453XGlaucoma is a neurodegenerative disease, which results in characteristic visual field defects. Intraocular pressure (IOP) remains the main risk factor for this leading cause of blindness. Recent studies suggest that disturbances in neurovascular coupling (NVC) may be associated with glaucoma. The resultant imbalance between vascular perfusion and neuronal stimulation in the eye may precede retinal ganglion cell (RGC) loss and increase the susceptibility of the eye to raised IOP and glaucomatous degeneration. Caveolin-1 (Cav-1) is an integral scaffolding membrane protein found abundantly in retinal glial and vascular tissues, with possible involvement in regulating the neurovascular coupling response. Mutations in Cav-1 have been identified as a major genetic risk factor for glaucoma. Therefore, we aim to evaluate the effects of Cav-1 depletion on neurovascular coupling, retinal vessel characteristics, RGC density and the positive scotopic threshold response (pSTR) in Cav-1 knockout (KO) versus wild type C57/Bl6 mice (WT). Following light flicker stimulation of the retina, Cav-1 KO mice showed a smaller increase in perfusion at the optic nerve head and peripapillary arteries, suggesting defective neurovascular coupling. Evaluation of the superficial capillary plexus in Cav-1 KO mice also revealed significant differences in vascular morphology with higher vessel density, junction density and decreased average vessel length. Cav-1 KO mice exhibited higher IOP and lower pSTR amplitude. However, there was no significant difference in RGC density between Cav-1 KO and wild type mice. These findings highlight the role of Cav-1 in regulating neurovascular coupling and IOP and suggest that the loss of Cav-1 may predispose to vascular dysfunction and decreased RGC signaling in the absence of structural loss. Current treatment for glaucoma relies heavily on IOP-lowering drugs, however, there is an immense potential for new therapeutic strategies that increase Cav-1 expression or augment its downstream signaling in order to avert vascular dysfunction and glaucomatous change.Jing Hong LooYing Shi LeeChang Yi WoonVictor H. K. YongBingyao TanBingyao TanBingyao TanLeopold SchmettererLeopold SchmettererLeopold SchmettererLeopold SchmettererLeopold SchmettererRachel S. ChongRachel S. ChongFrontiers Media S.A.articleglaucomaneurovascular couplingcaveolinneuroprotectionneurovascular dysfunctionNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glaucoma neurovascular coupling caveolin neuroprotection neurovascular dysfunction Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	glaucoma neurovascular coupling caveolin neuroprotection neurovascular dysfunction Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Jing Hong Loo Ying Shi Lee Chang Yi Woon Victor H. K. Yong Bingyao Tan Bingyao Tan Bingyao Tan Leopold Schmetterer Leopold Schmetterer Leopold Schmetterer Leopold Schmetterer Leopold Schmetterer Rachel S. Chong Rachel S. Chong Loss of Caveolin-1 Impairs Light Flicker-Induced Neurovascular Coupling at the Optic Nerve Head
description	Glaucoma is a neurodegenerative disease, which results in characteristic visual field defects. Intraocular pressure (IOP) remains the main risk factor for this leading cause of blindness. Recent studies suggest that disturbances in neurovascular coupling (NVC) may be associated with glaucoma. The resultant imbalance between vascular perfusion and neuronal stimulation in the eye may precede retinal ganglion cell (RGC) loss and increase the susceptibility of the eye to raised IOP and glaucomatous degeneration. Caveolin-1 (Cav-1) is an integral scaffolding membrane protein found abundantly in retinal glial and vascular tissues, with possible involvement in regulating the neurovascular coupling response. Mutations in Cav-1 have been identified as a major genetic risk factor for glaucoma. Therefore, we aim to evaluate the effects of Cav-1 depletion on neurovascular coupling, retinal vessel characteristics, RGC density and the positive scotopic threshold response (pSTR) in Cav-1 knockout (KO) versus wild type C57/Bl6 mice (WT). Following light flicker stimulation of the retina, Cav-1 KO mice showed a smaller increase in perfusion at the optic nerve head and peripapillary arteries, suggesting defective neurovascular coupling. Evaluation of the superficial capillary plexus in Cav-1 KO mice also revealed significant differences in vascular morphology with higher vessel density, junction density and decreased average vessel length. Cav-1 KO mice exhibited higher IOP and lower pSTR amplitude. However, there was no significant difference in RGC density between Cav-1 KO and wild type mice. These findings highlight the role of Cav-1 in regulating neurovascular coupling and IOP and suggest that the loss of Cav-1 may predispose to vascular dysfunction and decreased RGC signaling in the absence of structural loss. Current treatment for glaucoma relies heavily on IOP-lowering drugs, however, there is an immense potential for new therapeutic strategies that increase Cav-1 expression or augment its downstream signaling in order to avert vascular dysfunction and glaucomatous change.
format	article
author	Jing Hong Loo Ying Shi Lee Chang Yi Woon Victor H. K. Yong Bingyao Tan Bingyao Tan Bingyao Tan Leopold Schmetterer Leopold Schmetterer Leopold Schmetterer Leopold Schmetterer Leopold Schmetterer Rachel S. Chong Rachel S. Chong
author_facet	Jing Hong Loo Ying Shi Lee Chang Yi Woon Victor H. K. Yong Bingyao Tan Bingyao Tan Bingyao Tan Leopold Schmetterer Leopold Schmetterer Leopold Schmetterer Leopold Schmetterer Leopold Schmetterer Rachel S. Chong Rachel S. Chong
author_sort	Jing Hong Loo
title	Loss of Caveolin-1 Impairs Light Flicker-Induced Neurovascular Coupling at the Optic Nerve Head
title_short	Loss of Caveolin-1 Impairs Light Flicker-Induced Neurovascular Coupling at the Optic Nerve Head
title_full	Loss of Caveolin-1 Impairs Light Flicker-Induced Neurovascular Coupling at the Optic Nerve Head
title_fullStr	Loss of Caveolin-1 Impairs Light Flicker-Induced Neurovascular Coupling at the Optic Nerve Head
title_full_unstemmed	Loss of Caveolin-1 Impairs Light Flicker-Induced Neurovascular Coupling at the Optic Nerve Head
title_sort	loss of caveolin-1 impairs light flicker-induced neurovascular coupling at the optic nerve head
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ffd6621db4be44f3bb54166ce463c018
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Loss of Caveolin-1 Impairs Light Flicker-Induced Neurovascular Coupling at the Optic Nerve Head

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