Biomedical subjects

Colm O'Brien

Publications and source records attributed to Colm O'Brien.

7 recordsLinked to original sources

PubMed2006

Vasospasm in glaucoma: clinical and laboratory aspects.

During the last decade, the presumed etiology of glaucoma has moved from a pure pressure concept to a combined mechanical and vascular theory. Evidence of a localized vascular insufficiency leading to perfusion deficits of ocular structures, including the optic nerve head, the retina, the choroid, and the retrobulbar vessels, is now clear. This article evaluates the role of vasospasm as the primary cause of such a vascular failure. The role of both ocular and systemic vasospasms and their clinical correlations are discussed. At a cellular level, the function of the modulating role of the vascular endothelium is reviewed. Evidence of abnormalities of the vascular endothelium and its vasoactive peptides as a conduit for vasospasm is mounting. Herein lies exciting prospects for potential pharmacologic targets in future glaucoma management.

Blood Flow Velocity↗

PubMed2005

Pulsatile flow increases the expression of eNOS, ET-1, and prostacyclin in a novel in vitro coculture model of the retinal vasculature.

PURPOSE: By the development of a novel retinal microvascular endothelial and pericyte cell coculture system, this study determined the effects of pulsatile flow on the activation of the endothelial cell markers nitric oxide (NO), prostacyclin (PGI2), and endothelin (ET)-1. METHODS: Monocultured bovine retinal endothelial cells (BRECs) and cocultured BRECs with bovine retinal pericytes (BRPs) were exposed to low flow (flow rate, 0.3 mL/min; pulse pressure, 6 mmHg; shear stress, 0.5 dyne/cm2) or high flow (flow rate, 25 mL/min; pulse pressure, 56 mmHg; shear stress, 23 dynes/cm2) for 24 hours, by using a novel perfused transcapillary culture system. The cells were characterized by immunohistochemistry and electron and confocal microscopy. Endothelial nitric oxide synthase (eNOS) and phosphorylated-eNOSSer1179 (pp-eNOS) were determined by Western blot analysis. Nitrate, PGI2, and ET-1 levels were quantified in the medium perfusate by using fluorometric and enzyme-linked immunosorbent assays, respectively. Activation of cyclooxygenase (COX)-2 in BRECs was determined by measuring COX-2 promoter activity with a luciferase reporter assay. RESULTS: The presence of BRPs and BRECs was confirmed by Western blot, immunocytochemistry, and scanning electron microscopy. Phosphorylated eNOS (pp-eNOS) protein levels in BRECs were significantly increased from low to high flow in both mono- and cocultures, concomitant with a significant increase in nitrate levels in the conditioned medium after exposure to pulsatile flow. In parallel cultures, PGI2 levels were also significantly enhanced concomitant with an increase in the transactivation of a COX-2 promoter BREC after exposure to pulsatile flow. ET-1 levels were also increased in both mono- and cocultured cells. conclusions. In this study a novel, functioning, in vitro model of retinal microvascular endothelial and pericyte cells that respond to changes in pulsatile flow was established.

Animals↗

PubMed2004

Chronic systemic hypoxia causes intra-retinal angiogenesis.

Retinal hypoxia occurs in many conditions that cause vascular disease in the eye and is an important stimulus to new vessel formation. However, the adult retina can also become hypoxic when there is systemic hypoxaemia such as occurs in chronic lung diseases, congenital cardiac disease and residence at high altitude. Little is known about the adaptive responses of the retinal vasculature in such circumstances. Previous research in the retinopathy of prematurity model may not apply to the adult tissue given the different mechanisms controlling angiogenesis in developing and mature circulations. We tested the hypothesis that chronic systemic hypoxia leads to angiogenesis in the adult retinal circulation, in the absence of pre-existing vascular disease. Adult male Sprague-Dawley rats (n=9) were exposed to a fraction of inspired oxygen of 0.10 for 2 weeks while control animals (n=10) were exposed to room air. Stereological techniques were used to quantify the vascular volume, endothelial surface area and the total number of branch points of all blood vessels in the superficial retinal vascular plexus. The mean volume and endothelial surface area of these vessels were significantly greater in the hypoxic than in the control group. The mean number of blood vessel branch points was also significantly greater in the hypoxic group. Our findings demonstrate that chronic systemic hypoxia, in the absence of other pathological processes, causes angiogenesis in the adult rat retina and provide an in vivo model for investigating this important process in the adult retina, in particular pathways specific to this tissue.

Animals↗

PubMed2003

Pulsatile ocular blood flow in primary open-angle glaucoma and ocular hypertension.

PURPOSE: To compare pulsatile ocular blood flow measurements in untreated ocular hypertensive (OHT) subjects and primary open-angle glaucoma (POAG) patients. DESIGN: A prospective observational study in an institutional setting. METHODS: A total of 97 subjects were recruited to the study (50 ocular hypertensives, 24 glaucoma patients, and 23 normal subjects). "High-risk" OHT had intraocular pressure (IOP) > 25 mm Hg; "low-risk" OHT had IOP <or= 25 mm Hg. Pulsatile ocular blood flow (POBF) measurements were made with a pneumotonometer in sitting, standing, and supine positions. Intraocular pressure was measured with Goldmann tonometry. Twenty-six patients were started on topical treatment to reduce intraocular pressure, and the measurements were repeated at a review visit. RESULTS: Untreated POAG patients and high-risk OHT had reduced POBF (P <.001) and pulse volume (P <.001) compared with both normals and low-risk OHT. Women had higher POBF than men (P =.009, two-way analysis of variance). Subjects with pharmacologically lowered IOP had a significant increase in mean POBF (+80.9 microl/min, P =.02) and a significant reduction in mean arterial blood pressure (-11.0 mm Hg, P =.003). Postural reduction in POBF (from sitting to supine) increased and became statistically significant in POAG and OHT subjects on treatment (P <.0001). CONCLUSION: High-risk ocular hypertensives have reduced POBF when compared with low-risk ocular hypertensives and normals and do not differ significantly from POAG patients. Our findings support the clinical impression that ocular hypertensive subjects with IOP of over 25 mm Hg should be monitored closely and may benefit from prophylactic treatment to lower intraocular pressure.

Aged↗

PubMed2003

Quality of life in glaucoma and its relationship with visual function.

PURPOSE: The aims of this study were (a) to explore patients self-reported visual disability resulting from glaucoma by means of a questionnaire developed for this purpose; (b) identify activities strongly associated with a measure of visual field loss, (c) to quantify different psychophysical aspects of visual function; (d) to assess the relationship between objective measures of visual function and patients' perception of their vision-related quality of life. PATIENTS AND METHODS: Three groups of glaucoma patients (n = 47) with mild (n = 18), moderate (n = 19), and severe visual field loss (n = 10) and a group of normal controls (n = 19) underwent a comprehensive clinical examination, completed a questionnaire and, on a separate visit, performed a number of psychophysical tests of visual function. MAIN OUTCOME MEASURES: Questionnaire responses (vision-related quality of life, general health and psychosocial variables), visual acuity, visual fields, Esterman binocular disability scores, contrast sensitivity, critical flicker frequency, color vision, dark adaptation, glare disability (brightness acuity), and stereoacuity scores were measured. RESULTS: Fifteen of the 50 questions were noted to have a strong significant relationship with a measure of visual field loss and were included in a new questionnaire scale, the Glaucoma Quality of Life - 15 (GQL-15). The scale validity showed a significant correlation with perimetric mean deviation (MD) values (r = -0.6; P < 0.0001), the reliability of the scale was high (Cronbach alpha = 0.95), and test-retest reliability of the questionnaire was strong (r = 0.87). An overall statistically significant decrease in performance-related quality of life was noted between normal subjects and all groups of glaucoma patients. A significant relationship was found between the scale questionnaire summary performance measure and a number of psychophysical tests: Pelli-Robson contrast sensitivity (r = -0.45, P < 0.001), glare disability (r = -0.41, P < 0.001), Esterman binocular visual field test (r = -0.39, P < 0.001), dark adaptation (r = 0.34, P = 0.007), and stereopsis (r = 0.26, P = 0.04). CONCLUSION: Perceived visual disability relating to certain tasks (particularly involving dark adaptation and disability glare, activities demanding functional peripheral vision such us tripping over and bumping into objects and outdoor mobility tasks) was significantly associated with the severity of binocular visual field loss. As a result, a new glaucoma-specific questionnaire scale with good performance characteristics is presented in this study. The difficulties encountered by patients in everyday life (as measured with the questionnaire) were also mirrored in their performance on a number of psychophysical tests, especially contrast sensitivity, glare disability, Esterman binocular visual field test, and dark adaptation.

Aged↗

PubMed2003

Altered peripheral sensitivity to glucocorticoids in primary open-angle glaucoma.

PURPOSE: Increased levels of glucocorticoids are associated with raised intraocular pressure (IOP). The activity of glucocorticoids is regulated at a prereceptor level by 11beta-hydroxysteroid dehydrogenases (11beta-HSD). This study was an investigation of the central and peripheral sensitivity to glucocorticoids in patients with POAG or ocular hypertension (OHT) and the differential metabolism of glucocorticoids by 11beta-HSDs. METHODS: Patients with POAG or OHT and normal control subjects were studied. Peripheral sensitivity to glucocorticoids was assessed as dermal blanching and central sensitivity by dexamethasone suppression testing. Daily production rates of glucocorticoids were determined by quantifying metabolites in 24-hour urine. Plasma cortisol levels were determined at baseline (9 AM) and after an overnight low-dose dexamethasone suppression test. In a separate study, plasma and aqueous humor cortisol levels were determined in patients with POAG and normal subjects. RESULTS: Patients with POAG exhibited a greater cutaneous vasoconstrictor response to glucocorticoids than patients with OHT and normal subjects (20.7 +/- 3.1 vs. 8.5 +/- 4.4 and 8.6 +/- 4.5 arbitrary units, respectively; P < 0.05 in each case). Total glucocorticoid production rates were not different between groups, nor were total circulating cortisol levels before or after suppression of the hypothalamic-pituitary-adrenal axis by dexamethasone or concentrations in aqueous humor. The ratio of urinary cortisol to cortisone metabolites was elevated in POAG versus normal control and OHT (1.74 +/- 0.13 vs. 1.34 +/- 0.11 and 1.32 +/- 0.14; P < 0.05 in each case), indicating a change in the balance of 11beta-HSDs, without a change in other metabolic pathways. CONCLUSIONS: Patients with POAG exhibit increased peripheral vascular sensitivity to glucocorticoids. Increased sensitivity of glucocorticoid receptors, may enhance local glucocorticoid action in the eye and exacerbate the adverse effects of glucocorticoids in this condition.

Administration, Oral↗

PubMed2002

Systemic vascular endothelial cell dysfunction in normal pressure glaucoma.

AIM: Vascular risk factors, and particularly vasospasm, are thought to play a part in the pathogenesis of normal pressure glaucoma (NPG). This study aimed to determine whether the function of systemic resistance arteries was altered in patients with NPG. METHODS: Contractile and relaxant function was assessed in arteries dissected from gluteal fat biopsies (11 NPG, 12 control) using small vessel myography. RESULTS: Responses to K(+) and noradrenaline were similar in patients and controls and were unaffected by endothelial removal. In contrast, responses to 5-hydroxytryptamine (5-HT; pD(2); 7.29 (SD 0.16) v 6.66 (0.19); p=0.03) and endothelin-1 (ET-1; pD(2), 9.12 (0.10) v 8.72 (0.13); p=0.03) were enhanced in arteries from patients with NPG. Removal of the endothelium enhanced responses to 5-HT (pD(2), 6.66 (0.19) v. 7.66 (0.08); p=0.003) and ET-1 (pD(2), 8.72 (0.13) v. 9.66 (0.39); p=0.02) in control arteries but not in those from patients. ET-1 mediated contraction in control and patient arteries was reduced in the presence of (10(-5) M) nifedipine. Endothelium dependent and independent relaxation was not impaired in arteries from patients. CONCLUSIONS: This study has identified dysfunction of the systemic vascular endothelial cell in patients with normal pressure glaucoma. The vascular endothelium modulates contractile responses to 5-HT and ET-1 in human subcutaneous resistance arteries but this effect is lost in patients with NPG, indicating a selective defect in agonist mediated release of endothelium derived vasodilators. Selective antagonists of 5-HT and ET-1 may, therefore, help to prevent vasospasm in patients with NPG.

Adult↗