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At least 739 records · Page 41Linked to original sources

Suppression of ocular inflammation in endotoxin-induced uveitis by blocking the angiotensin II type 1 receptor.

PURPOSE: To examine whether the angiotensin II type 1 receptor (AT1-R) signaling plays a role in ocular inflammation in endotoxin-induced uveitis (EIU). METHODS: EIU was induced in C57BL/6 mice by a single intraperitoneal injection of 150 mug lipopolysaccharide (LPS). Tissue localization, mRNA expression, and protein levels of AT1-R in murine retinas were examined by immunohistochemistry, RT-PCR, and Western blot analyses, respectively. Telmisartan, an AT1-R antagonist widely used as an antihypertensive agent, was administered intraperitoneally at a dose of 10 mg/kg daily for 5 days until the injection of LPS. Twenty-four hours after administration, leukocyte adhesion to the retinal vasculature was evaluated with a concanavalin A lectin perfusion-labeling technique. Retinal mRNA and protein levels of intercellular adhesion molecule (ICAM)-1 were examined by RT-PCR and ELISA, respectively. Protein concentration and inflammatory cells in the aqueous humor were also measured. RESULTS: Retinal vessels were positive for AT1-R. In mice with EIU, retinal AT1-R mRNA and protein levels were significantly increased when compared to the normal control. EIU animals also showed significant increases in the number of inflammatory cells infiltrating the anterior chamber and adhering to the retinal vessels and in retinal ICAM-1 levels. Administration of telmisartan to EIU mice resulted in significant suppression of retinal ICAM-1 expression and leukocyte adhesion and infiltration compared with vehicle treatment. Protein concentration in the aqueous humor of telmisartan-treated EIU mice tended to be lower than that of vehicle-treated EIU mice, but the difference was not statistically significant. CONCLUSIONS: AT1-R signaling blockade inhibited retinal ICAM-1 upregulation and leukocyte adhesion and infiltration in the EIU model. These results suggest the potential use of an AT1-R antagonist as a therapeutic agent to reduce ocular inflammation.

Angiotensin II Type 1 Receptor Blockers↗

Retinal vascular changes and systemic diseases: corrosion cast demonstration.

The purpose of the present study is to clarify the specific retinal vascular changes in rat models of single spontaneous or hereditary systemic diseases. We used Wistar Kyoto (WKy) rats 6 months of age as normal controls, 24-month-old Wistar Kyoto rats in studies of aging, 16-month-old spontaneously hypertensive rats (SHR), 18-month-old rats with inherited hypercholesterolemia (RICO) for arteriosclerosis, and 18-month-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats for diabetes mellitus. Retinal vascular corrosion casts were made and observed with a scanning electron microscope. The retinal vessels were also examined with a transmission electron microscope. Specific changes in the retinal vessels were: narrowing and thin thread-like capillaries in aging; capillary tortuosity, irregularity and narrowing in hypertension; straightening in hypercholesterolemia; and loop formation and microaneurysms in diabetes mellitus. These specific changes in the retinal vessels in each systemic disease can be clearly and easily revealed in a three-dimensional fashion by corrosion casts followed by scanning electron microscopy.

Aging↗

Laser treatment and the mechanism of edema reduction in branch retinal vein occlusion.

PURPOSE: To test a hypothesis on the physiological mechanism of the disappearance of macular edema after laser treatment. The hypothesis is based on the effect grid laser treatment has on retinal oxygenation and hemodynamics. It predicts that laser-induced reduction of macular edema is associated with shortening and narrowing of retinal vessels in patients with branch retinal vein occlusion (BRVO). METHODS: The study included 12 subjects, treated with argon laser photocoagulation for BRVO and macular edema. Fundus photographs taken at the time of diagnosis and again after laser treatment, were digitized, and diameter and segment length of retinal vessels was measured using NIH-Image program. RESULTS: Macular edema disappeared or was dramatically reduced in all cases after laser treatment. The diameter of occluded venules constricted to 0.81+/-0.02 (mean +/- SD, P = 0.019) of the prelaser diameter and adjacent arterioles constricted to 0.78+/-0.01 (P = 0.008). The laser treatment also led to shortening of the affected vessels. The final segment length of the occluded venules was 0.95+/-0.17 (P = 0.005) of the length before treatment. The corresponding value for the adjacent arterioles is 0.95+/-0.14 (P = 0.008). Control arterioles and venules in the same fundus did not change in either length or width. CONCLUSIONS: These results do not reject the authors' hypothesis that the disappearance of macular edema in BRVO can be explained by the effect the laser photocoagulation has on retinal oxygenation. Increased oxygenation causes vessel constriction and shortening and lower intravascular pressure, which reduces edema formation according to Starling's law.

Aged↗

Intravenous administration of L-arginine increases retinal and choroidal blood flow.

PURPOSE: Nitric oxide (NO) is among the most important regulators of ocular perfusion. L-arginine, an amino acid, is the precursor of NO synthesis. The aim of the present study was to determine whether administration of L-arginine affects ocular blood flow. DESIGN: L-arginine (1 g/min) or placebo was administered intravenously for 30 minutes in 12 healthy volunteers in a randomized, double-masked, two-way cross-over design. METHODS: Ocular hemodynamics were measured before, in the last 10 minutes of the infusion period, as well as 30 minutes after cessation of the administration. Retinal vessel diameters were measured with a retinal vessel analyzer, red blood cell velocities with bidirectional laser Doppler velocimetry, and pulsatile choroidal blood flow was measured using laser interferometry. RESULTS: L-arginine significantly decreased mean arterial pressure by -8 +/- 5% and -6 +/- 7% at the two time points (P < .01), respectively. Intravenous administration of L-arginine increased choroidal blood flow by +10 +/- 6% and +12 +/- 7%, respectively. Retinal venous diameters decreased by -2.5 +/- 2.1% and -1.4 +/- 2.7%, respectively, whereas red blood cell velocity significantly increased after administration of L-arginine by +22 +/- 23% and +20 +/- 19% at the two time points. Thus, calculated blood flow in retinal veins, increased by +21 +/- 18% and +21 +/- 19% before and after the end of L-arginine infusion. CONCLUSIONS: Intravenous administration of L-arginine increases retinal and choroidal blood flow in healthy volunteers. Whether this effect is related to an increased NO-production or an unidentified mechanism remains to be clarified. However, administration of L-arginine might be an interesting new approach to therapeutically increase ocular blood flow in ocular vascular disease.

Adult↗

Abnormal maturation of the retinal vasculature in type XVIII collagen/endostatin deficient mice and changes in retinal glial cells due to lack of collagen types XV and XVIII.

Type XVIII collagen is important in the early phase of retinal vascular development and for the regression of the primary vasculature in the vitreous body after birth. We show here that the retina in Col18a1-/- mice becomes densely vascularized by anomalous anastomoses from the persistent hyaloid vasculature by day 10 after birth. In situ hybridizations revealed normal VEGF mRNA expression, but the phenotype of collagen XVIII deficient mice closely resembled that of mice expressing VEGF120 and VEGF188 isoforms only, suggesting that type XVIII collagen may be involved in VEGF function. Type XVIII collagen was found to be indispensable for angiogenesis in the eye, as also oxygen-induced neovascularization was less intense than normal in the Col18a1-/- mice. We observed a marked increase in the amount of retinal astrocytes in the Col18a1-/- mice. Whereas the retinal vessels of wild-type mice are covered by astrocytes and the regressing, thin hyaloid vessels are devoid of astrocytes, the retinal vessels in the Col18a1-/- mice were similarly covered by astrocytes but not the persistent hyaloid vessels in the vitreous body. Interestingly, double null mice lacking type XVIII collagen and its homologue type XV collagen had the persistent hyaloid vessels covered by astrocytes, including the parts located in the vitreous body. We thus hypothesize that type XV collagen is a regulator of glial cell recruitment around vessels and that type XVIII collagen regulates their proliferation.

Animals↗

Characterisation of the neovascularisation process in diabetic retinopathy by means of fractal geometry: diagnostic implications.

The neovascularisation formation and regression process of the peripheral retina in diabetic retinopathy was studied by means of fractal analysis. The fractal dimension of the local retinal vessel pattern was calculated to be significantly lower before formation of relevant neovascularisations than 2.5 years later, after formation of strong preretinal neovascularisations. Another year later the new vessels had regressed partially and the fractal dimension was again significantly reduced. This behaviour is almost independent of the representation of the vessel thickness during calculation. Since the retinal vasculature is a fractal, the fractal dimension appears as the "natural" measure of proliferative retinal vessel changes. It is demonstrated that the fractal dimension can be applied to characterise proliferative diabetic retinopathy. These features offer the possibility for computer-driven ("automated") quantitative characterisation of the treatment effect in proliferative diabetic retinopathy and possibly automated detection of proliferative diabetic retinopathy in the future. The limitations of the method are discussed.

Diabetic Retinopathy↗

[The optics of retinal blood vessels and their significance for scanning laser Doppler flowmetry].

Recently, the scanning laser Doppler flowmetry (SLDF) has been developed as a standard method for the quantification of retinal blood flow. However, the measured quantities flow, volume, and velocity depend on the angle between the direction of the blood flow and of the light. The underlying theory assumes isotropic illumination of the vessel. This assumption, however, is not valid for light back-scattered from retinal vessels. This paper investigates the contribution of different pathways of the light to the SLDF signal by a Monte Carlo simulation. It is shown that the light measured on a vessel having a thickness of 50 microns is predominantly back-scattered from the blood inside the vessel, whereas the measurement on vessels 20 microns in diameter or less also includes light transmitted through the vessel.

Blood Flow Velocity↗

Retinal vascular microfolds in highly myopic eyes.

PURPOSE: Retinal microfolds attributable to retinal vessels were first observed after vitrectomy for myopic foveoschisis and were believed to indicate inward retinal traction, possibly leading to high myopia-specific retinal diseases. We report retinal microfolds in high myopia without vitrectomy. DESIGN: Observational case series. METHODS: This is an institutional study. Seven eyes of seven patients in which retinal microfolds were observed using optical coherence tomography (OCT) were included in the study. We used an OCT-ophthalmoscope to confirm the precise location of the microfolds. We also investigated the relationship between the presence of microfolds and subjective distortion detected by examination of the corresponding retinal area using the Amsler grid chart in three eyes. RESULTS: All microfolds detected by OCT coincided with the retinal vessels using the OCT-ophthalmoscope. The folds coincided only with the retinal arterioles in six eyes (86%) and with both arterioles and veins in one (14%). Subjective distortion was detected in the retinal area corresponding to the microfolds in two eyes (67%) but was not detected in one eye (33%). CONCLUSIONS: The incidence of retinal microfolds is 2.9%, and thus they are not uncommon in highly myopic eyes without vitrectomy. The coincident appearance of the folds and vessels suggests that inflexibility of the retinal vessels and retinal stretching attributable to ocular elongation may cause the microfolds. The presence of these microfolds indicates that inward retinal vascular traction could be common in highly myopic eyes.

Aged↗

Observations on the incidence and significance of linear irregularities in the course of major retinal blood vessels in the fundus of the rat.

The ophthalmoscopic examination of rats receiving drug administered by daily intravenous bolus injection for 6 months revealed an increase in the incidence and amplitude of linear irregularities in retinal blood vessels with a tendancy towards tortuosity which appeared to be related to treatment. Subsequent critical observation of groups of untreated rats, and rats dosed orally with a vasodilator suggest this phenomenum may be related to haemodynamic mechanisms; and that more attention should be given to the dose volume administered intravenously in this species to avoid the detection of such ocular artefacts.

Administration, Oral↗

[Morphometric analysis of retinal vascular endothelial cells in rats].

INTRODUCTION: In the present study, we observed the transformation of endothelial cells in the retinal vessel of normal rats and examined the relationship between morphometrical parameters and vessel calibers. MATERIALS AND METHODS: Retinal vessels of male Wistar-Kyoto rats were stained with an en face silver staining method and the vessel caliber, the axis of the cell oriented parallel to the longitudinal axis and to the transverse plane of the vessel, and the deviation angle of endothelial cells against the vessel axis were measured under a light microscope. RESULTS: As the vessel caliber increased, endothelial cells showed a tendency to extend along the longitudinal axis in the arterioles, but endothelial cells remained unchanged in the venules. The deviation angle of endothelial cells was nearly parallel to the vessel axis especially in the arterioles. CONCLUSIONS: Change in shape of endothelial cells in the retinal arterioles suggested a high shear stress in the large arterioles, and lower shear stress in the smaller arterioles with its decrease of caliber. In the venules, however, the cell shape was unchanged, and this suggests that the blood flow is fairly steady.

Animals↗

Optic disc morphology in eyes after nonarteritic anterior ischemic optic neuropathy.

PURPOSE: Parapapillary chorioretinal atrophy, neuroretinal rim loss, and a decrease of retinal vessel diameter have been described to occur in glaucomatous eyes. This study was conducted to evaluate the frequency and degree of these signs in nonarteritic anterior ischemic optic neuropathy (AION). METHODS: We evaluated morphometrically and compared stereo color optic disc photographs of 17 patients after AION, 184 patients with primary open-angle glaucoma, and 98 normal subjects. RESULTS: The optic disc area and retinal vessel diameter were significantly smaller and the visibility of the retinal nerve fiber bundles was significantly reduced in patients after nonarteritic AION compared with that of the normal subjects. The optic disc shape, area, and form of zones alpha and beta of the parapapillary chorioretinal atrophy and the size and form of the neuroretinal rim did not differ significantly between these two groups. In the group of eyes with glaucoma, the neuroretinal rim was significantly smaller and the parapapillary chorioretinal atrophy was significantly larger than in the group of eyes with AION. Visibility of the retinal nerve fiber bundles and retinal vessel caliber did not differ statistically between the eyes with AION and those with glaucoma. CONCLUSIONS: These results indicate that the parapapillary chorioretinal atrophy is not larger in eyes after nonarteritic AION compared with normal eyes. They show that the area and shape of the neuroretinal rim, as determined planimetrically, may not markedly change after nonarteritic AION. They confirm previous reports on a small optic disc size as a risk factor for nonarteritic AION. They agree with findings of a reduced retinal vessel caliber in eyes with optic nerve damage, independently of the cause.

Adult↗

Ophthalmoscopic visualization of the inferior ophthalmic vein through a chorioretinal coloboma.

PURPOSE/METHODS: In a patient with a coloboma of the optic nerve, inferior retina and choroid, and deep portions of the sclera, a retrobulbar vessel moved irregularly relative to the retinal vessels, which moved contiguously with the posterior globe. RESULTS/CONCLUSION: Fluorescein angiography showed the retrobulbar vessel filling slightly later than overlying retinal vessels. We conclude that the retrobulbar vessel was a vein situated inferiorly to the optic nerve.

Adult↗

Fibrinolytic properties of some optic nerve vessels.

The fibrinolytic activity of posterior ciliary arteries (PCA), dural vessels (DV), central retinal vessels (CRV), and pial plexus (PP) in 18 human eyes was studied by the fibrin-slide technique and PAS staining. Acitvity was measured on the basis of the minimal incubation time at which lysis appeared. A constant pattern of fibrinolytic activity was found. The PCA were the most active, followed by DV, CRV, and PP. With consideration of the assumed antithrombotic role of fibrinolysis, the results suggest that PCA are better protected against occlusion than CRV.

Aged↗