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Increased expression of angiotensin-converting enzyme in retinas of diabetic rats.

PURPOSE: The aim of this study was to examine the localization and the changes in the amount of angiotensin-converting enzyme (ACE) and the relationship between the renin-angiotensin (RA) system and vascular endothelial growth factor (VEGF)/VEGF-receptor system in the retinas of diabetic rats. METHODS: Immunohistochemical localization of ACE, VEGF, and VEGF-receptor fetal liver kinase-1 (Flk-1) was examined in cryosections of the retinas of streptozotocin-injected diabetic rats. A semi-quantitative comparison of diabetic rats with age-matched controls was also performed by counting the ACE- or Flk-1-positive vessels per microscopic field. RESULTS: ACE immunoreactivity was localized in the retinal vessel walls, and the percentages of ACE-positive vessels were significantly increased in the retinas of diabetic rats maintained 3 to 5 months. Both VEGF and Flk-1 signals increased simultaneously with the increment of ACE immunoreactivity. CONCLUSIONS: ACE, expressed in the retinal vessel walls, increases simultaneously with the increment of both VEGF and Flk-1 in the retinas of diabetic rats, suggesting that upregulation of ACE might play some role in the progression of diabetic retinopathy through the VEGF/VEGF receptor system.

Animals↗

Plasma total homocysteine and retinal vascular disease.

PURPOSE: Hyperhomocysteinaemia has been linked to macrovascular disease. Our aim was to investigate whether there is a relationship between fasting plasma total homocysteine levels and retinal vascular disease. METHODS: We measured the homocysteine levels in 70 patients with arterial or venous retinal vessel occlusion and compared them with the levels in 85 controls without evidence of ischaemic heart disease. Homocysteine levels were determined by high-performance liquid chromatography with electrochemical detection and compared after logarithmic transformation. RESULTS: Homocysteine levels were found by univariate analysis (unpaired two-tailed t-test) to be significantly higher in the group with retinal artery occlusion than the group with retinal vein occlusion (p = 0.045) and in both groups compared with controls (18.4 and 13.8 vs 9.5 mumol/l; p = 0.0002 and < 0.0001, respectively). The controls, however, were significantly younger than the subjects (51.5 +/- 15.4 vs 66.2 +/- 11.9 years; p < 0.0001), but analysis of the results by age revealed significant differences between the groups and controls for the seventh decade (vein occlusions, p = 0.05) and for the eighth decade (artery occlusions, p = 0.037). Subgroup analysis of the retinal vessel occlusion group revealed significant differences in mean blood pressure between those with branch retinal vein occlusions (175/100 mmHg) and both those with central retinal vein occlusions (155/88 mmHg) and those with retinal artery occlusions (157/86 mmHg). Both vein occlusion subgroups also differed significantly with regard to homocysteine levels, branch < central (12.2 +/- 1.3 vs 15.0 +/- 1.6 mumol/l, p = 0.03). Multiple linear regression analysis revealed significant relationships between homocysteine levels and the presence of retinal vessel occlusion (p = 0.0002), serum creatinine (p = 0.001) and age (p = 0.003), but not gender. CONCLUSIONS: We conclude that homocysteine may be a risk factor for retinal vascular disease and could be simply and cheaply treated with folate and vitamins B6 and B12.

Adult↗

Regional retinal blood flow and vascular autoregulation.

The temporal retina is larger than the nasal retina and contains the metabolically active fovea. The variation in the distribution of blood between the temporal and nasal retinal circulations was investigated in 15 healthy volunteers, and the autoregulatory capacity of the temporal and nasal circulations was quantitated using 60% oxygen in the inspired air. Retinal blood flow was determined from red cell velocity using laser Doppler velocimetry and retinal vessel diameter from retinal photographs using a digital image analysis system. Volume flow was lower in the nasal than the temporal circulation by 52.49% (p < 0.001). This is a consequence of both significantly smaller vessels (20.4%, p < 0.001) and slower blood velocity in the nasal circulation (24.64%, p = 0.003) compared with the temporal vessels. After breathing 60% oxygen for 10 minutes, there was significant vasoconstriction (temporal, 10.42 +/- 1.24%, p < 0.001; nasal, 7.66 +/- 1.48%, p < 0.001), slower red cell velocity (temporal, 27.10 +/- 3.92%, p < 0.001; nasal, 27.36 +/- 5.51%, p < 0.001) and a significant reduction in the volumetric flow rate (temporal, 41.16 +/- 3.64%, p < 0.001; nasal, 37.99 +/- 5.07%, p < 0.001). The reduction in the haemodynamic parameters was comparable in the temporal and nasal circulations, indicating similar autoregulatory capacity. Retinal vascular conductance was calculated from volume flow and retinal perfusion pressure. It was 53% larger in the temporal than the nasal circulations. This provides an index of the metabolic needs of the different regions of the retina.

Adult↗

Epivascular glia and paravascular holes in normal human retina.

We examined the retinal surface of 28 autopsy eyes by scanning electron microscopy (SEM). Glialike cells or their processes, arranged in rows, were observed along retinal vessels in 22 eyes. Additionally, there were clusters of glialike cells over retinal vessels in 8 eyes. These proliferations ranged from focal to extensive ones, the latter resulting in distinct preretinal membranes. Focal defects of the superficial retina along the vessel were noted in 6 of 28 eyes. Transmission electron microscopic study in 2 surgically enucleated eyes with normal retinae revealed epivascular retinal degeneration and thinning of Müller cells. Glial processes appeared to be covering the defect of the internal limiting membrane and some projections of these cells continued inwards. These findings were consistent with the SEM findings of epivascular glialike structure. Our conclusions are that epivascular glialike structures and paravascular surface defects appear as a common finding in normal senile eyes, and that occasionally membranous formations arise from the epivascular area.

Adult↗

Sheathotomy without separation of venule overlying arteriole at occlusion site in uncommon branch retinal vein occlusion.

Two cases of uncommon branch retinal vein occlusion (BRVO) with vein overlying artery at occlusion site that can be found in less than 1% who underwent retinal venule sheathotomy without separation of retinal vessel for decompression of BRVO were reported. Both patients had macular hemorrhage, edema, and area of macular capillary nonperfusion. Visual acuity (VA) worsened to 6/60 in both cases. The retinal venules were dissected around the crossing site without separation of retinal vessels. Intraoperative dilation, pulsation and restoration of downstream blood flow of the involved venules were observed. In the first patient, at 1 day, 2 weeks, and 6 weeks postoperatively, VA improved to 6/36, 6/9, and 6/6, respectively, and remained unchanged at 12 months postoperatively. In the second patient, VA improved to 6/24 on the first day postoperatively and improved to 6/18 at 1 week follow up and continuously improved to nearly normal at 2 months postoperatively then patient lost contact. Postoperative fundus fluorescein angiogram showed dilated and improved perfusion with decreased macular edema in both cases. Optical coherent tomography confirmed remarkable reduction of retinal thickness (from 874 microns preoperatively to 420 microns at 1 week postoperatively) in the second patient. Retinal venule sheathotomy without separation of retinal vessel for decompression of BRVO with venule overlying arteriole at occlusion site could be effective for improving VA and decreased macular edema.

Adult↗

Angiography with fluorescein-labeled dextrans in a primate model of uveitis.

Sequential fluorescein angiography, using fluorescein-labeled dextran molecules of several different sizes, was carried out in monkeys with intraocular inflammation induced with interphotoreceptor retinoid-binding protein. The vascular leakage seen with the dextrans was compared with that seen with standard fluorescein sodium angiography. The angiograms demonstrated that different-sized leaks appear in the retinal vessels in adjacent areas during the course of the inflammation. Most retinal vessels leaked only fluorescein sodium and no dextran of any size, suggesting that it is the unbound fluorescein that leaks out of these vessels and not fluorescein bound to plasma albumin. It was not possible to tell by clinical examination which areas would leak the larger-molecular weight tracers. Ultrastructural studies of the veins leaking the dextrans revealed areas of abnormal endothelial tight junctions, whereas the tight junctions were normal in areas where leakage occurred with fluorescein alone.

Animals↗

[Correlation of intra- and para-papillary glaucomatous changes--a planimetric study of 200 normal and 450 glaucoma eyes].

The zone "alpha" (irregular hypo- und hyperpigmentation) and "beta" (visible large choroidal vessels and visible sclera) of parapapillary chorioretinal atrophy had been measured in 450 eyes of 330 patients suffering from chronic primary open-angle glaucoma and in 200 normal eyes of 161 subjects. In the present study, the results were correlated with intrapapillary and other parapapillary parameters. Significant correlations (p less than 0.001) were found with: (1) the neuroretinal rim size; (2) the horizontal and vertical cup/disc ratios and the quotient; (3) the frequency of bared circumlinear and cilioretinal vessels and of optic disc hemorrhages, respectively; (4) the retinal vessel diameter; (5) the visibility of the retinal nerve fiber bundles; (6) the glaucoma stage. The parapapillary changes were most marked in the sector in which the neuroretinal rim notch was the largest and the narrowness of the retinal vessel caliber the most pronounced. The parapapillary glaucomatous changes in time and location correlated with the intrapapillary and other parapapillary alterations. They deserve special attention in the diagnosis of glaucoma.

Choroid↗

[Coats disease].

Coats disease is an idiopathic disorder characterized by an abnormal development of retinal vessels (telangiectasia), with a progressive deposition of intraretinal or subretinal exudates, leading to exudative retinal detachment. Classically is isolated, unilateral and affects mainly boys between 4 to 8 years. The diagnostic methods include direct and indirect opthalmoscopy, fluorescein angiography, ultrasonography, CT scan, MR imaging, especially în the advanced stages of disease, when is difficult to differentiate from retinoblastoma. The treatment includes laser therapy of abnormal leaking retinal vessels and cryotherapy în early stages, more advanced stages require surgical techniques of retinal reattachment. Stabilization of the disease course or clinical improvement can be achieved using a carefully selected therapy.

Adolescent↗

Segmentation of retinal blood vessels by combining the detection of centerlines and morphological reconstruction.

This paper presents an automated method for the segmentation of the vascular network in retinal images. The algorithm starts with the extraction of vessel centerlines, which are used as guidelines for the subsequent vessel filling phase. For this purpose, the outputs of four directional differential operators are processed in order to select connected sets of candidate points to be further classified as centerline pixels using vessel derived features. The final segmentation is obtained using an iterative region growing method that integrates the contents of several binary images resulting from vessel width dependent morphological filters. Our approach was tested on two publicly available databases and its results are compared with recently published methods. The results demonstrate that our algorithm outperforms other solutions and approximates the average accuracy of a human observer without a significant degradation of sensitivity and specificity.

Algorithms↗

Mechanism of retinal ganglion cell loss in inherited retinal dystrophy.

To study the inner retinal layers in RCS rats, which suffer major loss of retinal photoreceptors during the first 3 months of life, retinal ganglion cells (RGC) were labelled with fluorogold and their axons were immunoreacted with an antibody against neurofilaments. The retinal vessels were stained with horeseradish peroxidase and the RGC layer was stained with methylene blue. Animals more than 6 months of age showed areas devoid of fluorogold-labelled cells that extended from the optic disc to the periphery. The course of the RGC axons was also abnormal and showed tortuosities, dilatations and signs of abortive regeneration at sites where most inner retinal vessels cross the axons. We conclude that some months after photoreceptor degeneration has concluded in dystrophic animals, some retinal vessels compress the RGC axons and cause retrograde degeneration of their parent cells.

Animals↗

Recombinant tissue plasminogen activator injected into the vitreous cavity may penetrate the retinal veins of a porcine model of vascular occlusion.

AIM: To determine if recombinant tissue plasminogen activator (rtPA) injected into the vitreous cavity can penetrate the retinal vessels of porcine eyes with or without vascular occlusion. METHODS: Eight eyes (group I) of four pigs underwent clamping of the optic nerve flush with the globe for 90 minutes. One hour after reperfusion, one eye of each pig was injected with 75 microg of rtPA, and the fellow eye was injected with balanced salt solution (BSS). Eyes were processed for immunohistochemistry. Four additional eyes (group II) of two pigs were subjected to the same injections, but without optic nerve clamping. RESULTS: After reperfusion, the clinical picture was similar to that of a central retinal vein occlusion. Immunoperoxidase staining showed rtPA only in the retinal veins but not the retinal arteries in all eyes injected with rtPA in both groups I and II. Those eyes also showed intense rtPA staining at the level of the internal limiting membrane (ILM). No staining was seen at the level of the ILM or inside the retinal vessels in the BSS injected eyes. Immunofluorescence staining showed intense staining at the level of the ILM, but not inside the retinal vessels in the rtPA-injected eyes. CONCLUSIONS: rtPA may penetrate the retinal veins, but not the arteries of porcine eyes with and without vascular occlusion. The ILM may play a part in preventing rtPA penetration.

Animals↗

Retinal fluorescein leakage in retinitis pigmentosa.

Of 82 consecutive patients with retinitis pigmentosa, 78 underwent fluorescein angiography using standard and special, abbreviated photographic protocols. The stereoscopic angiograms disclosed alterations of the blood-retinal barrier, primarily at the level of the retinal pigment epithelium, in 60 patients. Areas of leakage were bilateral in all but two persons. The macula most frequently showed leakage, followed by the optic disk, the arcade areas, and the periphery. A few individuals exhibited leakage from the perifoveal retinal vessels. None of these patients had significant retinal vascular alterations or exudates in the retinal periphery. In eyes with no cataract or detectable macular pigment change and with comparable amounts of epiretinal membrane, the presence of macular edema was significantly correlated with reduced central visual acuity.

Adolescent↗

[Effect of photodynamic therapy with ATX-S 10 (Na) on experimental choroidal neovascularization].

PURPOSE: To evaluate an appropriate irradiative condition for selective occlusion of experimental choroidal neovascularization(CNV) with photodynamic therapy (PDT) using ATX-S 10 (Na). METHODS: Experimental CNV was induced in monkey eyes by laser photocoagulation. PDT(dose of irradiative energy 40 to 80J/cm2) was performed after 3.5 mg/kg of body weight intravenous injections of ATX-S 10(Na). CNV and retinal vessel occlusion induced by PDT was evaluated by fluorescein angiography (FA) at 1 and 7 days after irradiation. If FA showed no fluorescein dye leakage from CNV at 1 and 7 days after irradiation, CNV was evaluated by histopathological analysis at 7 days after irradiation. RESULTS: Within 30 to 33 minutes after ATX-S 10(Na) injection and irradiation with 50 to 60 J/ cm2, FA showed no fluorescein dye leakage from CNV and no closure of retinal vessels at 1 and 7 days after irradiation. Light micrographs showed occluded CNV, and retinal vessels remained patent and there was no apparent change in the inner layer of the retina. CONCLUSIONS: Irradiative condition of ATX-S10 (Na) 3.5 mg/kg was appropriate 30 to 33 minutes after ATX-S 10(Na) injection and irradiation with 50 to 60 J/cm2.

Animals↗

Protein Z levels and central retinal vein or artery occlusion.

OBJECTIVES: Central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO) are common disorders associated with risk factors for atherosclerosis. Protein Z is a cofactor for the inactivation of activated factor X (Xa) by the protein Z dependent protease inhibitor. Protein Z deficiency was recently linked to increased risk of arterial thrombosis. We investigated whether CRVO and CRAO are associated with low protein Z levels. PATIENTS AND METHODS: Patients with CRVO, CRAO or recurrent branch retinal vein occlusion were recruited to the study. Protein Z level, lupus anticoagulant (LAC), anticardiolipin antibodies (ACA) and activated protein C resistance (APCR) were determined in plasma from patients (n = 36) and healthy controls (n = 42). RESULTS: Thirty patients in the study group had traditional risk factors for retinal vessel occlusion and six patients had none. There was no significant difference in protein Z levels between the whole study group patients and controls (1995 +/- 810 vs. 2010 +/- 603 ng/mL, P = 0.922). However, patients with no risk factors for retinal vessel occlusion had significantly lower protein Z levels than controls (1379 +/- 682 vs. 2010 +/- 603 ng/mL, P = 0.022). Positive LAC was found in six patients and one control subject (P = 0.04). There were three patients and one control subject with abnormal APCR (P = 0.3) and none with positive ACA. Low protein Z level (lower than fifth percentile of control) was not associated with the presence of LAC or APCR. CONCLUSION: Low protein Z level may be another risk factor for retinal vessel occlusion in patients without traditional risk factors for these disorders.

Adult↗