Limited intravascular coupling in the rodent brainstem and retina supports a role for glia in regional blood flow

Kuo, Ivana Y.; Chan‐Ling, Tailoi; Wojcikiewicz, Richard J.H.; Hill, Caryl E.

doi:10.1002/cne.21873

Cited by 10 publications

(12 citation statements)

References 57 publications

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“…In the mouse retinal vasculature, Cx40 was localized to the primary arteries (Figure a) similar to the expression pattern in the rat retina (Kuo et al, ). In the high magnification images, Cx40 was expressed in string‐like structures, similar to Cx43 in relay regions.…”

Section: Resultssupporting

confidence: 68%

Domain‐specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina

Ivanova

Kovács-Öller

Sagdullaev

2019

J of Comparative Neurology

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In the retina, diverse functions of neuronal gap junctions (GJs) have been established. However, the distribution and function of vascular GJs are less clear. Here in the mouse retina whole mounts, we combined structural immunohistochemical analysis and a functional assessment of cellular coupling with a GJ‐permeable tracer Neurobiotin to determine distribution patterns of three major vascular connexins. We found that Cx43 was expressed in punctate fashion on astroglia, surrounding all types of blood vessels and in continuous string‐like structures along endothelial cell contacts in specialized regions of the vascular tree. Specifically, these Cx43‐positive strings originated at the finest capillaries and extended toward the feeding artery. As this structural arrangement promoted strong and exclusive coupling of pericytes and endothelial cells along the corresponding branch, we termed this region a “vascular relay.” Cx40 expression was found predominantly along the endothelial cell contacts of the primary arteries and did not overlap with Cx43‐positive strings. At their occupied territories, Cx43 and Cx40 clustered with tight junctions and, to a lesser extent, with adhesion contacts, both key elements of the blood–retina barrier. Finally, Cx37 puncta were associated with the entire surface of both mural and endothelial cells across all regions of the vascular tree. This combinatorial analysis of vascular connexins and identification of the vascular relay region will serve as a structural foundation for future studies of neurovascular signaling in health and disease.

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Section: Resultssupporting

confidence: 68%

Domain‐specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina

Ivanova

Kovács-Öller

Sagdullaev

2019

J of Comparative Neurology

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“…Hyperpolarization of an individual SMC can spread through endothelial cells and to smooth muscle cells via myoendothelial coupling and evoke a coordinated dilating response along the length of an arteriole (Zhang et al, 2011). Of note, the patterns of gap junctional staining within the rat retina shows regional specificity, suggesting a homogenous distribution of gap junction proteins Cxs37 and 40 expressed in large radiating arterioles but absent in smaller vessels (Kuo et al, 2008). …”

Section: Regulation Of Retinal Blood Flowmentioning

confidence: 99%

Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease

Kur

Newman

Chan‐Ling

2012

Progress in Retinal and Eye Research

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455

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We review the cellular and physiological mechanisms responsible for the regulation of blood flow in the retina and choroid in health and disease. Due to the intrinsic light sensitivity of the retina and the direct visual accessibility of fundus blood vessels, the eye offers unique opportunities for the non-invasive investigation of mechanisms of blood flow regulation. The ability of the retinal vasculature to regulate its blood flow is contrasted with the far more restricted ability of the choroidal circulation to regulate its blood flow by virtue of the absence of glial cells, the markedly reduced pericyte ensheathment of the choroidal vasculature, and the lack of intermediate filaments in choroidal pericytes. We review the cellular and molecular components of the neurovascular unit in the retina and choroid, techniques for monitoring retinal and choroidal blood flow, responses of the retinal and choroidal circulation to light stimulation, the role of capillaries, astrocytes and pericytes in regulating blood flow, putative signaling mechanisms mediating neurovascular coupling in the retina, and changes that occur in the retinal and choroidal circulation during diabetic retinopathy, age-related macular degeneration, glaucoma, and Alzheimer's disease. We close by discussing issues that remain to be explored.

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“…To date, Cx26 has not been detected in mouse or rat retina [11]. In human and rat retina, Cx43 is associated with blood vessels [12], [13] though recently, Cx30 and Cx43 have been shown to be associated only with superficial retinal blood vessels in the rat, not the deeper plexus [14], whilst Cx45 is found in cerebral smooth muscle cells [15] and rodent retinal neurons [16].…”

Section: Introductionmentioning

confidence: 99%

Connexin 30 Expression and Frequency of Connexin Heterogeneity in Astrocyte Gap Junction Plaques Increase with Age in the Rat Retina

et al. 2013

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We investigated age-associated changes in retinal astrocyte connexins (Cx) by assaying Cx numbers, plaque sizes, protein expression levels and heterogeneity of gap junctions utilizing six-marker immunohistochemistry (IHC). We compared Wistar rat retinal wholemounts in animals aged 3 (young adult), 9 (middle-aged) and 22 months (aged). We determined that retinal astrocytes have gap junctions composed of Cx26, -30, -43 and -45. Cx30 was consistently elevated at 22 months compared to younger ages both when associated with parenchymal astrocytes and vascular-associated astrocytes. Not only was the absolute number of Cx30 plaques significantly higher (P<0.05) but the size of the plaques was significantly larger at 22 months compared to younger ages (p<0.05). With age, Cx26 increased significantly initially, but returned to basal levels; whereas Cx43 expression remained low and stable with age. Evidence that astrocytes alter connexin compositions of gap junctions was demonstrated by the significant increase in the number of Cx26/Cx45 gap junctions with age. We also found gap junctions comprised of 1, 2, 3 or 4 Cx proteins suggesting that retinal astrocytes use various connexin protein combinations in their gap junctions during development and aging. These data provides new insight into the dynamic and extensive Cx network utilized by retinal astrocytes for communication within both the parenchyma and vasculature for the maintenance of normal retinal physiology with age. This characterisation of the changes in astrocytic gap junctional communication with age in the CNS is crucial to the understanding of physiological aging and age-related neurodegenerative diseases.

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Limited intravascular coupling in the rodent brainstem and retina supports a role for glia in regional blood flow

Cited by 10 publications

References 57 publications

Domain‐specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina

Domain‐specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina

Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease

Connexin 30 Expression and Frequency of Connexin Heterogeneity in Astrocyte Gap Junction Plaques Increase with Age in the Rat Retina

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