Microvascular endothelial function and severity of primary open angle glaucoma

Bukhari, Syed Mudassar Imran; Kiu, K Y; Sulong, Sarina; Rasool, Aida Hanum Ghulam; Liza-Sharmini, Ahmad Tajudin

doi:10.1038/eye.2016.185

Cited by 15 publications

(13 citation statements)

References 57 publications

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“…Elevated serum levels of ET-1 and other biochemical markers of endothelial function in the aqueous humor of glaucoma patients suggest that endothelial dysfunction is associated with disease pathology (Sugiyama et al, 1995;Noske et al, 1997;Resch et al, 2009a;Ghanem et al, 2011;Cellini et al, 2012;Li et al, 2016). There is a statistically significant correlation between microvascular endothelial function and severity of POAG in the Malay population (Bukhari et al, 2016). In patients, blocking both ET A and ET B receptors results in increased blood flow through the retina, choroid and ONH.…”

Section: Blood Flow Regulation Is Impaired In Glaucomamentioning

confidence: 99%

The Neurovascular Unit in Glaucomatous Neurodegeneration

Wareham

Calkins

2020

Front. Cell Dev. Biol.

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Glaucoma is a neurodegenerative disease of the visual system and leading cause of blindness worldwide. The disease is associated with sensitivity to intraocular pressure (IOP), which over a large range of magnitudes stresses retinal ganglion cell (RGC) axons as they pass through the optic nerve head in forming the optic projection to the brain. Despite clinical efforts to lower IOP, which is the only modifiable risk factor for glaucoma, RGC degeneration and ensuing loss of vision often persist. A major contributor to failure of hypotensive regimens is the multifactorial nature of how IOP-dependent stress influences RGC physiology and structure. This stress is conveyed to the RGC axon through interactions with structural, glial, and vascular components in the nerve head and retina. These interactions promote pro-degenerative pathways involving biomechanical, metabolic, oxidative, inflammatory, immunological and vascular challenges to the microenvironment of the ganglion cell and its axon. Here, we focus on the contribution of vascular dysfunction and breakdown of neurovascular coupling in glaucoma. The vascular networks of the retina and optic nerve head have evolved complex mechanisms that help to maintain a continuous blood flow and supply of metabolites despite fluctuations in ocular perfusion pressure. In healthy tissue, autoregulation and neurovascular coupling enable blood flow to stay tightly controlled. In glaucoma patients evidence suggests these pathways are dysfunctional, thus highlighting a potential role for pathways involved in vascular dysfunction in progression and as targets for novel therapeutic intervention.

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Section: Blood Flow Regulation Is Impaired In Glaucomamentioning

confidence: 99%

The Neurovascular Unit in Glaucomatous Neurodegeneration

Wareham

Calkins

2020

Front. Cell Dev. Biol.

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“…Compared to normal subjects, glaucoma patients exhibit blood flow abnormalities in vessels of the optic nerve head, 18 retina, 18 retrobulbar tissue, 19 and choroid. 18 , 20 , 21 With limited information regarding autonomic dysfunction involvement, several researchers proposed that ocular vessel disturbances are linked to plasma levels of endothelin-1, 22 systemic blood pressure, 23 , 24 and vasospasm. 25 Autonomic function reflects the effect of parasympathetic nervous system activity on the heart.…”

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confidence: 99%

Autonomic Dysfunction and Blood Pressure in Glaucoma Patients: The Lifelines Cohort Study

Asefa

Neustaeter

Jansonius

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Purpose We investigated relationship of glaucoma with measurements related to autonomic dysfunction, including heart rate variability (HRV) and blood pressure (BP). Methods Glaucoma was defined using a questionnaire-based algorithm for 86,841 LifeLines Cohort Study participants. Baseline HRV (root mean square of successive differences [RMSSD]) was calculated from resting electrocardiograms; systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) were oscillometric-based measurements. We used a generalized linear mixed model, adjusted for age, age square, sex, body mass index, and familial relationships to assess the relationship of baseline HRV and BP (continuous and quartiles), hypertension, and antihypertensive medication with glaucoma at follow up (median, 3.8 years). Results The odds ratio (OR) of glaucoma was 0.95 (95% confidence interval [CI], 0.92–0.99) per unit increase in log-transformed RMSSD (in ms), indicating that autonomous dysfunction (low HRV) is associated with a higher risk of glaucoma. Per 10-mm Hg increase in BP, we found ORs of 1.03 (95% CI, 1.01–1.05; P = 0.015) for SBP, 1.01 (95% CI, 0.97–1.05; P = 0.55) for DBP, 1.03 (95% CI, 1.00–1.06; P = 0.083) for MAP, and 1.04 (95% CI, 1.01–1.07; P = 0.006) for PP. The OR for the lowest versus highest RMSSD quartile was 1.15 (95% CI, 1.05–1.27; P = 0.003). The ORs for the highest versus second quartile were 1.09 (95% CI, 0.99–1.19; P = 0.091) for SBP and 1.13 (95% CI, 1.02–1.24; P = 0.015) for PP. Glaucoma was more common among hypertensives (OR, 1.25; 95% CI, 1.16–1.35; P < 0.001); among those using angiotensin-converting enzyme (ACE) inhibitors (OR, 1.35; 95% CI, 1.18–1.55; P < 0.001); and among those using calcium-channel blockers (OR, 1.19; 95% CI, 1.01–1.40; P = 0.039). Conclusions Low HRV, high SBP, high PP, and hypertension were associated with glaucoma. Longitudinal studies may elucidate if autonomic dysregulation and high BP also predict glaucoma incidence.

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“…In the current study, we observed endothelial dysfunction of retinal arterioles and structural changes in retinal tissue of I/R-treated pigs. Recent studies have been more and more focused on the association between endothelial dysfunction and the severity of vision-threatening diseases like primary open angle glaucoma and diabetic retinopathy due to the important role of an intact endothelium for proper regulation of retinal perfusion [26,27,28]. In the present study, retinal arteriole dilation after I/R was blunted in response to the endothelium-dependent vasodilator, bradykinin, but not to the endothelium-independent vasodilator, SNP, indicative of endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Short-Time Ocular Ischemia Induces Vascular Endothelial Dysfunction and Ganglion Cell Loss in the Pig Retina

Zadeh

García-Bardon

Hartmann

et al. 2019

IJMS

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Visual impairment and blindness are often caused by retinal ischemia-reperfusion (I/R) injury. We aimed to characterize a new model of I/R in pigs, in which the intraocular pathways were not manipulated by invasive methods on the ocular system. After 12 min of ischemia followed by 20 h of reperfusion, reactivity of retinal arterioles was measured in vitro by video microscopy. Dihydroethidium (DHE) staining, qPCR, immunohistochemistry, quantification of neurons in the retinal ganglion cell layer, and histological examination was performed. Retinal arterioles of I/R-treated pigs displayed marked attenuation in response to the endothelium-dependent vasodilator, bradykinin, compared to sham-treated pigs. DHE staining intensity and messenger RNA levels for HIF-1α, VEGF-A, NOX2, and iNOS were elevated in retinal arterioles following I/R. Immunoreactivity to HIF-1α, VEGF-A, NOX2, and iNOS was enhanced in retinal arteriole endothelium after I/R. Moreover, I/R evoked a substantial decrease in Brn3a-positive retinal ganglion cells and noticeable retinal thickening. In conclusion, the results of the present study demonstrate that short-time ocular ischemia impairs endothelial function and integrity of retinal blood vessels and induces structural changes in the retina. HIF-1α, VEGF-A, iNOS, and NOX2-derived reactive oxygen species appear to be involved in the pathophysiology.

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Microvascular endothelial function and severity of primary open angle glaucoma

Cited by 15 publications

References 57 publications

The Neurovascular Unit in Glaucomatous Neurodegeneration

The Neurovascular Unit in Glaucomatous Neurodegeneration

Autonomic Dysfunction and Blood Pressure in Glaucoma Patients: The Lifelines Cohort Study

Short-Time Ocular Ischemia Induces Vascular Endothelial Dysfunction and Ganglion Cell Loss in the Pig Retina

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