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Blood-retinal barrier after blunt trauma to the eye.

The competence of blood retinal barrier at the level of retinal pigment epithelium (RPE) and retinal capillaries was studied 30 min, 24 h, 3 days, and 7 days after experimental blunt eye injury in the pig, using horseradish peroxidase (HRP). Leakage of HRP into the outer retinal layers was observed in association with disrupted RPE in the first three days after injury. No HRP leakage was seen 7 days after the trauma and the retinal vessels remained competent throughout the study. It is suggested that extracellular edema occurs in the early stages of commotio retinae due to the disruption of blood retinal barrier at the level of the RPE.

Animals↗

Immunohistochemical distribution of basic fibroblast growth factor in experimental retinal ischaemia and reperfusion in the rat.

It has been proposed that basic fibroblast growth factor (basic FGF) mediates the neovascular response in a variety of conditions, including diabetic retinopathy and branch retinal vein occlusion. To test the hypothesis that basic FGF was released from retinal stores as a result of retinal ischaemia, transient retinal ischaemia was induced, followed by 48 h of reperfusion, in the rat by combined central retinal vasculature and optic nerve ligation. The immunolocalization of basic FGF was studied in the retina. We found that basic FGF in the normal retina is present around the deeper retinal vessels and in the neuronal tissue of the outer plexiform layer. In the eyes that had ischaemia followed by reperfusion, there was moderate cellular oedema with retinal swelling, and mitoses in the inner nuclear and plexiform layers. There were no changes evident at the immunohistochemical level either in the intensity or distribution of stores of basic FGF. We conclude from these data that stores of basic FGF are not altered dramatically under the conditions of transient experimental ischaemia and reperfusion in the rat, despite the presence of cellular proliferation.

Animals↗

[Wyburn-Mason syndrome].

BACKGROUND: There are various malformations of retinal vessels. Some of them are associated with cerebral vascular anomalies. MATERIALS AND METHODS: This report is given on a girl 6 years of age with a retinal racemose angioma. RESULTS: The clinical examination showed a unilateral racemose angioma combined with retinachorioidal anastomosis and a hemifacial vascular malformation. We found teleangiectasia in this area. The ophthalmoscopy demonstrated a blurred border of optic disc on the right eye with forward protrusion of the disc about + 2.0 dioptres. Large racemose lesions may be localized to the optic nerve and may involve segmental areas of the macula. The ultrasound showed a papillary stasis with highly reflective structures. The ultrasonic patterns are interpreted as a cholesterosis or fibrovascular tissue. This findings may belong to the rare Wyburn-Mason syndrome. Acute neurological symptoms by similar lesions the midbrain and hemorrhages during extraction of teeth are reported in literature.

Child↗

Exudative retinal detachment after photodynamic injury.

Exudative retinal detachments occur in a variety of retinal and choroidal diseases. We created serous retinal detachment in the cat eye by means of photodynamic injury produced by activation of intravascular rose bengal using filtered, focused light (550 nm). Fluorescein angiography later revealed focal retinal and choroidal vascular occlusion surrounded by a larger area of leakage through the pigment epithelium. Serous retinal detachments occurred rapidly, gradually enlarged over the next 3 days, and resolved in all eyes after 14 to 21 days. Histopathologic and ultrastructural features of early lesions included the accumulation of proteinaceous fluid in the subretinal space, pigment epithelial cell damage, and localized occlusion of retinal vessels and the choriocapillaris. Later changes consisted of limited regeneration of the retina and portions of the tapetum. In several respects, these experimental detachments resemble the serous retinal detachments associated with choroidal ischemia in humans, and may serve as a useful model in the study of choroidal microvascular hypoperfusion.

Animals↗

New technique to demonstrate the network of blood capillaries of the human retina in their three-dimensional arrangement.

A method is presented that demonstrates the whole network of the blood capillaries of the human retina, making it possible (using a dark-field microscope at high magnification) to view the three-dimensional arrangement of this network in different planes by moving the drive of the microscope. The basic principle includes filling the vascular system with oxygen in statu nascendi by injection of H2O2 into the vitreous body of the intact eye and achieving fixation of the retinal tissue by application of a mixture of H2O2 and ethanol, and rendering the dry and flat retinal preparation transparent by soaking it in a specially prepared resin. The retinal vessels are made visible in an optically empty dark field by diffraction of light in a gas-filled specimen. This method allows preparation of the human retinal vasculature in simply enucleated eyes without cannulation of the central retinal artery and, therefore, it may be appropriate to support pathological and anatomical investigations.

Arterioles↗

A combination of microendoscopy and spectrophotometry allowing real-time analysis of microcirculatory parameters during in vivo observations.

A combination of microendoscopy (which is a modification of endoscopy with fine rigid endoscopes) and spectrophotometry (which analyses on line the remission spectra from the endoscopic picture) is presented. This setup allows the endoscopic in vivo observation of haemodynamics as well as simultaneous on line determination of intravascular haemoglobin oxygenation. Furthermore, the clearance of intravasally applied tracers can be analysed. Application, results and further evaluation of this new technique are demonstrated in the retinal vessels of the albino rabbit.

Animals↗

Effects of neuropeptides on the sumatriptan-disturbed circulation in the optic nerve head of rabbits.

The purpose of this work was to study 'in vivo' the vascular responses of retinal vessels of New Zealand white rabbits to substance P (SP), neurokinin A (NKA), neurokinin B (NKB), senktide, capsaicin (CAPS), and calcitonin gene related peptide (CGRP) before and after selective antagonist administration. We examined the effects of these neuropeptides on the normal circulation in the optic nerve head of the rabbit. Drugs were injected via pars plana through a micropipette system. Ten minutes before perivascular injection of 10 nmol/l sumatriptan (to contract the vessel), a selective antagonist or its solvent was administered. Then, cumulative injection of the agonist was performed. The other eye was used as control. Direct measurement of retinal arteriole diameters was performed using digital angiography. The quantification of the relaxing effect is expressed as percentage related to the precontracted vascular diameter. Microinjection of SP (NK1 receptor agonist) up to 10 nmol/l induced a dose-dependent arteriolar dilating effect [E(max) (mean +/- SEM) 21.3 +/- 2.3%]. After the perivascular preinjection of 1 nmol/l L-668,169 or 1 nmol/l L-733,060 (NK1 receptor antagonists), the SP dose-response curve was shifted to the right. The same results were obtained with NKA (NK2 receptor agonist) which induced the most potent effect of all neuropeptides (E(max) 53.3+/-2.5%). The NK2 receptor antagonists L-659,877 and GR 159897 (1 nmol/l) strongly inhibited this arteriolar vasodilation. As for CGRP, doses up to 10 nmol/l induced a marked vasodilation (E(max) 41.1+/-0.4%) which decreased after microinjection of the selective antagonist CGRP8-37. The NK3 receptor agonists (senktide and NKB) showed a minor vasodilating effect (E(max) 5.1+/-1.2 and 8.0+/-0.9%, respectively). On the contrary, CAPS showed a marked dose-dependent vasodilating effect (E(max) 43.2+/-2.9%), antagonized by the tachykinin receptor antagonists and CGRP8-37. These results suggest, for the first time, the presence of NK1, NK2, and CGRP receptors on the retinal arteriolar wall of the rabbit.

Animals↗

Retinal microcirculation as revealed by SEM corrosion casts in the rat.

The morphology of the retinal microcirculation has been extensively studied by different techniques. Nevertheless, some problems concerning the capillary bed lamination and pre- and postcapillary patterns have not yet been clarified. In the present study the SEM corrosion cast technique was employed to study the three-dimensional relationships of rat retinal vessels and to follow the smallest vascular branches. Rat retina is considered a useful experimental model for a number of pathologies which affect the microvascular bed deeply. Two precapillary patterns have been observed. Precapillary arterioles gave rise to capillaries both as terminal branches or as collaterals. The former pattern of ramification allows only a regulation of flow in a whole group of capillaries downstream, the latter pattern could provide a finer regulation of blood flow. SEM corrosion casts have shown very well the lamination of the capillary bed: one can easily realize this by seeing the overlapped meshes of the two different planes, vessels in between the two capillary laminae can always be followed from one meshwork to the other. This three-dimensional organization is an interesting model for retinal circulation because it shows many features in common with the retina of humans and primates.

Animals↗

Blood-retinal barriers in health and disease.

The blood-retinal barrier (BRB) is located at two levels, forming an outer barrier in the retinal pigment epithelium and an inner barrier in the endothelial membrane of the retinal vessels. Both these membranes have tight junctions of the 'non-leaky' type and cellular transport processes predominate. The occurrence of an alteration of the BRB in retinal disease is briefly reviewed. Fluorescein angiography findings have now been extended by the introduction of vitreous fluorophotometry. Kinetic vitreous fluorophotometry studies in diabetes and in experimental situations suggest that measurement of the coefficient of fluorescein loss from the vitreous may be the best means of evaluating the early functional changes which occur in the BRB in diabetes and their apparent reversibility.

Animals↗

[The macular vascular changes in diabetic retinopathy].

The angiofluorographic surveys done on 46 patients with diabetes shows some particular modifications of the retinal vessels, from the foveolar, perifoveolar and parafoveolar areas. These modifications influence the values of the visual acuity; they are not connected in all cases with all the retinal vascular modifications.

Adult↗

Central and peripheral arteriovenous passage times of the retina in glaucoma.

The purpose of this paper was to estimate arteriovenous passage (AVP) times, taking into account the non-uniform distribution of arrival times over the vessel diameter, and assessment of respective differences between 15 normal controls (N), 30 primary open-angle glaucoma (POAG) and 30 normal-pressure glaucoma (NPG) patients. Arrival times in retinal vessels were assessed from digitized scanning laser fluorescein angiograms. The arrival times were assessed as a function of position (juxtamural versus axial) in the vessel. This differentiation, based on the measurement position in the vessel, enabled the estimation of AVP times of the posterior pole and of the peripheral retina. The overall, juxtamural and axial AVP times were prolonged in POAG as compared to both N and NPG (P<0.03). The difference in axial AVP times between POAG and normal subjects was considerably larger than the juxtamural values. The distribution of AVP times was considerably larger in POAG patients than in N subjects and NPG patients. Retinal AVP times are prolonged in POAG patients as compared to N and NPG. The wider distribution of AVP times in POAG patients may point to a generalized microvascular alteration. Since the axial AVP times seem to provide the largest differences between NPG and POAG patients, this measurement may be preferred over more general AVP times. The axial AVP times may possibly reflect peripheral vascular changes, e.g. increased vascular resistance. The underlying mechanisms causing these differences are at present unknown.

Blood Circulation↗

Heterogeneity in collagen biosynthesis by sprouting retinal endothelial cells.

Bovine retinal microvascular endothelial cells can display two distinct and reversible morphologies in culture: 'cobblestone' and 'sprouting'. The cobblestone morphology resembles the resting cells lining the lumen of mature vessels while the sprouting morphology resembles the angiogenic cells involved in the formation of new vessels. Retinal cells displayed some heterogeneity in the shape of the cells making up the cobblestone monolayer. In contrast, all cell lines displayed an identical sprouting morphology. We have investigated the synthesis of matrix macromolecules by retinal endothelial cells displaying either the cobblestone or the sprouting morphology. Type IV was the only collagen synthesised by eight different lines of early-passage (between one and six) cobblestone endothelial cells. Collagen types I and III were not detected in these cultures. In contrast, heterogeneity was observed in the types of collagen synthesized by four lines of early-passage cells displaying the sprouting morphology. That is, two lines synthesised collagen types, II, III and IV, whereas two other lines continued to synthesise only type IV collagen. Both cobblestone and sprouting cells synthesised fibronectin and thrombospondin, although the relative amounts of these macromolecules varied with culture conditions. The pattern of collagen synthesis by cobblestone cells was also affected by in vitro "ageing": 4/5 lines examined above passage eight synthesised collagen types I, III and IV. Our results indicate that there is heterogeneity in the sprouting phenotype displayed by retinal endothelial cells, and that this phenotype is not necessarily associated with the synthesis of type I collagen. We suggest that differences in the spectrum of matrix macromolecules synthesised by sprouting endothelial cells may play a role in the control of angiogenesis.

Animals↗

TNF-alpha is critical for ischemia-induced leukostasis, but not retinal neovascularization nor VEGF-induced leakage.

Vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-alpha) show significant overlap with regard to their effects in the eye. It has been postulated that VEGF-induced leukostasis, breakdown of the blood-retinal barrier, and ischemia-induced retinal neovascularization may be mediated, at least in part, through TNF-alpha. In this study, we used mice deficient in TNF-alpha to test our hypothesis. Compared to wild type mice, TNF-alpha-deficient mice showed an 80% reduction in leukocyte accumulation in retinal vessels after intravitreous injection of VEGF, and 100% reductions after intravitreous injections of interleukin-1beta (IL-1beta) or platelet-activating factor (PAF). The increase in retinal vascular permeability induced by injection of PAF was significantly reduced in mice lacking TNF-alpha, but VEGF- and IL-1beta-induced leakage was unaffected. Compared to wild type mice with oxygen-induced ischemic retinopathy, TNF-alpha-deficient mice with ischemic retinopathy showed significantly reduced leukostasis and mild reduction in vascular leakage, but no significant difference in retinal neovascularization. These data suggest that TNF-alpha mediates VEGF-, IL-1beta-, and PAF-induced leukostasis and vascular leakage mediated by PAF, but not leakage caused by VEGF or IL-1beta. Ischemia-induced retinal neovascularization, which has previously been shown to require VEGF, does not require TNF-alpha and is unaffected by attenuation of leukostasis.

Animals↗

Indocyanine green angiographic findings in acute retinal necrosis.

PURPOSE: To clarify indocyanine green (IA) angiographic features in patients with acute retinal necrosis (ARN). METHODS: Two patients with ARN were examined by fluorescein angiography (FA) and IA, and findings from both were compared. RESULTS: Fundus examination revealed widespread retinal hemorrhages and yellowish-white patches in the periphery, characteristic of ARN. In both cases, FA showed diffuse dye leakage from all retinal veins and the optic disc, and vascular obstruction in the peripheral fundus. In IA, dye leakage was localized, and extravasation of dye was evident only from the lower temporal retinal vein and the lower half of the optic disc. This pattern of indocyanine green dye leakage appeared to be continuous from the optic disc toward the lower temporal retinal vein. Also, IA clearly demonstrated choroidal vascular filling delay in one case in the early phase of the angiogram. CONCLUSIONS: While FA showed diffuse dye leakage from all retinal veins, IA identified only the retinal vessels with the most prominent vascular damage. IA also identified choroidal vascular lesions in these patients with ARN. The information obtained by IA might be useful to detect retinal vasculitis with prominent inflammation and to determine the extent of choroidal inflammation in patients with ARN.

Acyclovir↗

The in vivo effect of endothelins on retinal circulation in nondiabetic and diabetic rats.

PURPOSE: The endothelins are potent vasoactive peptides. This study was performed to characterize the in vivo effects of the endothelin peptides on the retinal circulation in nondiabetic and diabetic rats. METHODS: The video fluorescein angiography methodology was used to quantitate retinal hemodynamic responses to endothelin-1 (ET-1) and endothelin-3 (ET-3) in rats. A total of 99 rats were used for these experiments. Video fluorescein angiography recordings were performed before and at different times after intravitreal injection of different concentrations of ET-1 and ET-3 in nondiabetic and diabetic rats. Vascular diameters and retinal circulation times were determined using computer-assisted image analysis of the recorded angiograms. RESULTS: The maximal response to ET-1 was observed at 15 minutes after intravitreal injection and was maintained for as long as 30 minutes after injection. Subsequent data measured at 15 minutes after intravitreal injection showed significant prolongation of retinal circulation times and retinal artery constriction. For example, at a concentration of 10(-7) M, the retinal circulation time increased by 270% +/- 121% of the baseline value. In contrast, 10(-7) M ET-3 injection showed a 52% +/- 29.5% increase in circulation time compared to baseline. In diabetic animals, 10(-7) M ET-1 injection showed a blunted response (only 26% +/- 8% of baseline) compared to the same ET-1 injected concentration in nondiabetic rats. CONCLUSIONS: The rat retinal circulation shows a pronounced retinal response to ET-1 intravitreal injection. The response to ET-3 is significantly less than it is to ET-1, and in diabetic animals there was also a significant blunting of the retinal response to ET-1. The blunted response to ET-3 is consistent with the lower affinity of retinal vessel ET-1 receptors to ET-3. The blunted ET-1 response in diabetic rats is consistent with previously reported results, demonstrating resistance to ET-1 action in retinal pericytes exposed to high glucose.

Animals↗

Effects of oxygen and carbon dioxide on human retinal circulation.

PURPOSE: Carbogen, a gas mixture of 95% O2 and 5% CO2, is given to patients with retinal artery obstruction in an attempt to improve retinal oxygenation. The purpose of this study was to compare the effects of carbogen and 100% O2 breathing on retinal blood flow. METHODS: On two separate occasions, 12 normal, healthy volunteers breathed air and then either 100% O2 or carbogen while laser Doppler velocimetry measurements and monochromatic fundus photographs were taken. Retinal vessel diameter, maximum velocity of red blood cells, and volumetric blood flow rate were determined in a main temporal vein. RESULTS: Both 100% O2 and carbogen caused significant average reductions in vessel diameter (14.1% and 10.6%, respectively), maximum red blood cell velocity (42.1% and 27.3%, respectively), and blood flow (56.4% and 42.2%, respectively). The average vasoconstriction of the large retinal veins caused by carbogen was not significantly smaller than that caused by 100% O2. The average reductions in maximum red blood cell velocity and blood flow caused by carbogen were significantly smaller than those caused by 100% O2 (P < .001 and P < .01, respectively). CONCLUSIONS: In normal subjects, inhalation of carbogen leads to less reduction in blood flow than inhalation of 100% O2, presumably by reducing the vasoconstriction of small arterioles induced by elevated oxygen levels.

Adult↗

Dysversion of the optic disc and axial length measurements in a presumed amblyopic population.

PURPOSE: Our purpose was to evaluate anatomic variations of eyes presumed to be amblyopic. METHOD: Computer imaging and photography of the optic discs of 205 amblyopic subjects were performed and the axial lengths of 183 of the subjects were measured. The paired optic nerve images were evaluated for symmetry of disc contours and orientation of central blood vessels to detect optic nerve head dysversion. Dysversion of the optic nerve head, which is also referred to as segmental hypoplasia, is a congenital disorder characterized by the central retinal vessels emerging temporal to the vertical midline of the disc and being directed nasally or the nerve head tilting in a vertical direction resulting in a downward or oblique tilting of the discs with the blood vessels emerging at the superior or inferior disc rim. RESULTS: Ninety-three subjects had optic nerve dysversion. There was a greater degree of anisometropia (P< or =.004) in subjects with dysversion (anisometropia factor of 2.51+/-2.15) than in the subjects with symmetric discs (anisometropia factor of 1.76+/-1.63). Axial lengths of the amblyopic eyes were significantly smaller (P<.0001) than those of the nonamblyopic eyes. There was no statistical difference (P< or =.879) in length between amblyopic eyes with dysversion and those with symmetric discs. CONCLUSION: Optic disc dysversion was identified in 45.4% of patients who were previously assumed to be amblyopic. There are anatomic malformations in the eyes of a significant proportion of the presumed amblyopic population. This suggests that, in these individuals, congenital peripheral factors rather than impaired cortical development may be responsible for decreased unilateral acuity.

Adolescent↗

Unilateral atrophy of the optic nerve associated with retrograde and anterograde degenerations in the visual pathways in Slc: Wistar rats.

Unilateral degenerative atrophy of the optic nerve (ON) occurred in 6 of 80 male and 4 of 80 female Slc: Wistar rats. Two of these cases completely lost the intracranial portion of the unilateral ON and the remainder had the small ON. The optic disc and ON were located histologically in the posterior pole of the eyeball of 2 rats with no intracranial ON. ON lesions in all cases were characterized by a reduced number of axons with a small number of myelinated axons and marked astrogliosis. There were also swelling, fragmentation and spheroid formation of axons, as well as thickening of the connective tissue sheaths and vessel walls in the ON. One side of the optic chiasma and optic tract contralateral to the affected ON reduced in volume, became degenerated and were accompanied by gliosis. Focal or diffuse degeneration of the retina was observed in the eyeballs with affected ON. Retinal ganglion cells decreased in the number showing chromatolysis. These retinae became thin and developed degeneration of both inner and outer portions with sclerotic changes in the retinal vessels. The ophthalmic and ciliary arteries in the eyeballs with affected ON often developed proliferative or occlusive endoarteritis, suggesting that retinal lesions may have resulted not only from axonal degeneration in the ON but also from ischemia. Histologic lesions suggestive of transneuronal degeneration were found in the contralateral lateral geniculate body and rostral colliculus. Based on the data presented, it was presumed that a primary lesion may have been induced in the ON by a circulatory disturbance and followed by retrograde and anterograde degenerations in the visual pathways.

Animals↗