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[Changes in retinal hemodynamics in old age].

The influence of increasing age on the haemodynamics of the retina was examined in a prospective study using 377 consecutive videoangiograms. A significant alteration of the arm-to-retina time and the arterial, capillary and venous phases of the retinal circulation is not detectable before the 60th year of life. After the age of 60 all circulation times change in a negative sense. A further, pronounced slowing of retinal circulation appears after the 75th year of life. This shows that the well-known morphological alterations in the retinal vessels in old age are accompanied by haemodynamic changes.

Adult↗

Degenerated intramural pericytes ('ghost cells') in the retinal capillaries of diabetic rats.

One of the earliest histopathological signs of diabetic retinopathy is a selective loss of intramural pericytes from retinal capillaries. In the present study, the retinal vessels of rats with streptozotocin-induced diabetes (STZ Wistar) and rats with genetically-induced insulin dependent diabetes mellitus (BB Wistar) and non-insulin dependent diabetes mellitus (SHR/N-corpulent) were examined after 6 to 8 months duration for diabetes-related retinal microangiopathies. The SHR/N-corpulent (cp) rats were fed a 54% sucrose diet, whereas the STZ Wistar and BB Wistar rats were fed laboratory chow for 32 to 36 weeks. In all the diabetic rats, the retinal capillaries in enzyme-digested flat mounts exhibited an increase in periodic-acid-Schiff (PAS) staining and loss of pericytes compared to their respective euglycemic controls. Pericyte "ghosts", like those defined in human diabetes as intramural pockets lacking normal cell contents, were documented by high resolution micrographs in all the diabetic rats. Endothelial cell proliferation, capillary dilation, and varicose loop formation were noted in some of the diabetic rats. Hence, similar capillary lesions were found in very different groups of diabetic rats. The findings suggest that a chronic high tissue concentration of glucose is the underlying factor which triggers pathogenesis in the pericyte. Hyperglycemia-induced activation of endogenous aldose reductase of the polyol pathway is probably the initial insult, but other factors such as advanced glycosylation products may affect the final outcome.

Animals↗

Haemolytic-uraemic syndrome with thrombotic microangiopathy of the retina following cytomegalovirus infection: postmortem findings.

Haemolytic-uraemic syndrome is characterized by thrombotic microangiopathy of the glomeruli and smaller arterial vessels of the kidney. Extrarenal thrombotic microangiopathy occurs, but ocular involvement is rarely demonstrated microscopically. We describe a 33 year old woman with a 3 week febrile episode and seropositivity for cytomegalovirus infection who developed acute renal failure, blindness and severe encephalopathy which was the cause of death. Thrombotic microangiopathy of retinal vessels may be more common than is expected from the literature. The exclusion of ocular structures in postmortem examinations explains the lack of anatomoclinical correlation.

Adult↗

Comparison of lectin reactivity in the vessel beds of the rat eye.

The capillary beds of the eye are lined by two types of endothelia, fenestrated in the choriocapillaris and ciliary body, and continuous in the retina and iris. In this study, we wished to find a marker for each of these types of vessel beds using lectin histochemistry. Sections of glutaraldehyde fixed rat eyes embedded in epoxy resin were extracted with sodium ethoxide and rehydrated. Binding of 15 different lectins was visualized using the avidin-biotin peroxidase technique. We found WGA, WGA-s, LFA and PHA-E to strongly bind retinal vessels. In addition to the above lectins, iris vessels bound GSL-I. Choriocapillaris reacted variably only with WGA and not at all with other lectins tested. Vessels of ciliary body processes did not react with any lectin studied. The less fenestrated vessels of the base of the ciliary process bound lectins similar to the retina. We speculate that the differential lectin staining of the various vessel beds of the eye may reflect the degree of fenestration of the endothelium. This reactivity may be influenced by variations in the surrounding milieu including cells and extracellular matrix.

Animals↗

Fluorescein angiography in reticular degeneration of the pigment epithelium.

We studied reticular degeneration of the pigment epithelium by fluorescein angiography in 32 eyes of 50 consecutive patients who had ophthalmoscopic indications of this aging-related entity. In this type of degeneration, fluorescein angiography delineated extensive abnormalities of the retinal pigment epithelium and demonstrated normal-appearing retinal vessels and choriocapillaries in the affected areas.

Aged↗

[Retinal vasculopathy associated with Berger's IgA nephropathy].

AIM: Ophthalmological complications associated with Berger's IgA nephropathy comprise scleritis, episcleritis, keratoconjunctivitis as well as anterior uveitis. We present a new association of IgA nephropathy with a retinal vasculopathy. METHODS: Presentation of two clinical cases. RESULTS: Two patients presented with hematuria and epistaxis associated with a retinal vasculopathy characterised by teleangiectasies, capillary occlusion with retinal hemorrhages, neovascularisations and macular edema with decreased visual acuity. Fluorescein angiography showed zones of non-perfusion as well as vasculitic changes. A general medical exam revealed a normal arterial pressure but a slightly elevated creatinine. Immunological investigations for the presence of antibodies showed no positive results. Renal biopsy demonstrated mesangial proliferations with diffuse deposits of IgA. Over the course of a 2 year follow-up some of the retinal changes regressed under treatment with cortisone and visual acuity returned to normal. The teleangiectasies showed no progression. CONCLUSION: Berger's IgA nephropathy can be associated with a retinal vasculopathy which may be due to local deposition of IgA immune complexes in the retinal vessels.

Adult↗

Low oxygen consumption in the inner retina of the visual streak of the rabbit.

The oxygen requirements of different retinal layers are of interest in understanding the vulnerability of the retina to hypoxic damage in retinal diseases with an ischemic component. Here, we report the first measurements of retinal oxygen consumption in the visual streak of the rabbit retina, the region with the highest density of retinal neurons, and compare it with that in the less-specialized region of the retina underlying the vascularized portion of the rabbit retina. Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of retinal depth in anesthetized animals. Measurements were performed in the region of the retina containing overlying retinal vessels and in the center of the visual streak. Established mathematical analyses of the intraretinal oxygen distribution were used to quantify the rate of oxygen consumption in the inner and outer retina and the relative oxygen contributions from the choroidal and vitreal sides. Outer retinal oxygen consumption was higher in the visual streak than in the vascularized area (means +/- SE, 284 +/- 20 vs. 210 +/- 23 nl O2.min(-1) x cm(-2), P = 0.026, n = 10). However, inner retinal oxygen consumption in the visual streak was significantly lower than in the vascular area (57 +/- 4.3 vs. 146 +/- 12 nl O2 x min(-1) x cm(-2), P < 0.001). We conclude that despite the higher processing requirements of the inner retina in the visual streak, it has a significantly lower oxygen consumption rate than the inner retina underlying the retinal vasculature. This suggests that the oxygen uptake of the inner retina is regulated to a large degree by the available oxygen supply rather than the processing requirements of the inner retina alone.

Animals↗

Determination of retinal blood velocity with respect to the cardiac cycle using laser-triggered release of liposome-encapsulated dye.

A system of selective angiography has been developed for measuring blood velocity in retinal arteries and veins. It uses a liposome-encapsulated fluorescent dye that is released by application of laser energy in a specific retinal vessel. The method is shown to be able to distinguish between peak systolic velocity and minimum diastolic velocity. In the cynomolgus monkey, the two values were found to differ by approximately a factor of three. It is known that many ocular and systemic diseases affect retinal circulation, and therefore a method of blood velocity measurement with such sensitivity may prove highly valuable in the practice of ophthalmology. As an example, the velocity in a retinal vein was measured before and after partial occlusion by photocoagulation. The two values obtained were significantly different, and the blood velocity was found to return to the value prior to occlusion when measured at 18 days.

Animals↗

Contractile proteins in retinal endothelium and other non-muscle tissues of the eye.

The present study is the first investigation to demonstrate, by employing the combined approach of immunologically and electron microscope methods, the presence of actin-like contractile proteins in the mammalian retina, the corneal epithelium and endothelium, the iris, and the ciliary body, and to confirm their presence in lens epithelium. This is also the first report to demonstrate by these methods the presence of microfilaments and intermediate filaments in retinal vascular endothelium. Since we have shown that actin filaments are especially abundant in immature retinal endothelial cells, the question of their function arises, and we have discussed their possible relevance to the closure of immature retinal vessels when exposed to hyperoxia.

Actins↗

Immunogold localization of basement membrane molecules in rat retinal capillaries.

Vascular basement membrane contains laminin, fibronectin, proteoglycan and collagens. These molecules have been identified in various tissues by immunolabeling methods and biochemical analyses. We have previously localized laminin, fibronectin and type IV collagen to the basement membrane of rat retinal vessels at the ultrastructural level using an immunoperoxidase method. In this study, we use an immunogold method to re-examine the distribution of these molecules and also to study the localization of heparan sulfate proteoglycan and types I, III and V collagen in the retinal capillary basement membrane. Gold labeling for laminin, type IV collagen and proteoglycan were found diffusely on the basement membrane of the endothelium and pericyte, while that for fibronectin and type V collagen was spotty and variable and that for types I and III collagen was negligible. The segment of basement membrane between the endothelial cell and pericyte appeared less reactive to anti-laminin and anti-type IV collagen than the membrane between the pericyte and perivascular neuroretina. The immunogold method may be useful in quantitative studies of thickened basement membranes under abnormal conditions.

Animals↗

Fundus abnormalities in a patient with type I Gaucher's disease with 12-year follow-up.

PURPOSE: To report a case of type I Gaucher's disease with rare presentation of fundus abnormalities in long-term observation. DESIGN: Observational case report. METHODS: This 53-year-old Taiwanese woman suffered from type I Gaucher's disease for 12 years, with initial presentation of hepatoslpenomegaly in 1992. RESULTS: At that time, poor vision with unusual macular change and peripheral retinal vessel leakage was also noted. She received a complete ophthalmic examination at the initial visit and again 12 years later in 2003. She was treated with imiglucerase injection during the last 4 years. However, her visual acuity was 10/200 in both eyes. The macular and peripheral retinal degenerative change progressed after 12 years. CONCLUSIONS: Fundus changes associated with Gaucher's disease are uncommon. We should not neglect the possibility of retinal involvement and progression in these patients.

Capillary Permeability↗

Validation of scanning laser Doppler flowmetry for retinal blood flow measurements in animal models.

PURPOSE: To evaluate the validity of scanning laser Doppler flowmetry in retinal blood flow measurement in vivo using rabbit and monkey eyes and the microsphere technique. METHODS: A commercially available scanning laser Doppler flowmeter (SLDF), pigmented rabbits and cynomolgus monkeys were used. In rabbits, SLDF measurements at a retinal field approximately one papillary diameter away from the optic nerve head where discrete retinal vessels were not visible (vascularized medullary field) were compared with those at a field approximately one papillary diameter below the ONH (nonvascularized extramedullary field). The effect of intraocular pressure (IOP) on SLDF measurements was studied by elevating the IOP manometrically in both rabbit and monkey eyes. Retinal and choroidal blood flow measurements using the microsphere technique and an SLDF measurements were performed simultaneously in the same rabbit eye before and 30 min after 0.3 mg/kg intravenous injection of lomerizine, a calcium antagonist, or intravitreal injection of 20 microl of 10(-6) M endothelin-1. RESULTS: The blood flow measurement with an SLDF (SLDF flow) obtained from the medullary field in rabbits were 304 +/- 63 in an arbitrary unit (n = 24), while 392 +/- 39 in the extramedullary field. SLDF flow did not significantly changed by changes in IOP when it was below 50 mmHg, significantly decreasing with IOP elevation above that level in rabbits and a similar tendency was also seen in monkeys. It showed a significant correlation with retinal blood flow measured by the microsphere technique (r = 0.596, P < 0.0001) in rabbits; no correlation was found with the choroidal blood flow rate (r = 0.021, P > 0.1). CONCLUSIONS: SLDF measurements is thought to mainly reflect retinal circulation in rabbits and monkeys.

Animals↗

Histopathologic features of neovascularization in sickle cell retinopathy.

PURPOSE: To examine the histopathologic and morphometric features of neovascular lesions in human proliferative sickle cell retinopathy. METHODS: Postmortem ocular tissue was obtained from three subjects (aged 20, 28, and 40 years) with SS hemoglobinopathy and prepared for adenosine diphosphatase flat-embedding. Morphometric analysis was performed before serial sectioning. RESULTS: Numerous active and autoinfarcted lesions were found that represented virtually all stages in the life cycle of preretinal neovascularization. These formations ranged from single small loops extending from arteries and veins along the retinal surface to the typical complex, elevated sea fan formations. Sea fans developed at hairpin loops and at arteriovenous crossings. There was an average of 5.6 connections between sea fans and retinal vessels; of these, 45% were arteriolar, 52.5% were venular, and 2.6% were at the capillary level. Six of eight sea fans were located at arteriovenous crossings. Autoinfarction appeared to occur initially within the sea fan capillaries. The average height of sea fans was 123 microns above the retinal surface. CONCLUSIONS: Preretinal neovascularization in sickle cell retinopathy can arise from both the arterial and venous sides of the retinal vasculature and can assume a variety of morphologic configurations. Multiple feeding arterioles and draining venules are common, and autoinfarction appears to occur initially at the preretinal capillary level rather than at feeding arterioles. Arteriovenous crossings may be a preferential site for sea fan development.

Adult↗

Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans.

PURPOSE: Increased leukocyte-endothelium interaction have been suggested as a phenomenon contributing to capillary occlusion and/or rupture of the blood-retina barrier during human retinal vascular diseases. This study was performed to evaluate if fluorescein-labeled autologous leukocytes (FLALs) can be used for examination of leukocyte transit in the human retina. METHODS: The preparation consisted of human dextran-separated leukocytes mixed with fluorescein. After reinjection in normal subjects and in one diabetic patient, a confocal scanning laser ophthalmoscope was used to visualize them in the retinal circulation. The changes between FLALs and control leukocytes in the expression of leukocytes adhesion molecules CD11b and CD62L were evaluated by flow cytometry. RESULTS: The circulating FLALs were clearly visible in retinal vessels. The mean (+/- SD) capillaries velocity was 1.43 (+/- 1.3) mm/s in the macula and 1.82 (+/- 1.4) mm/s in the peripapillary area. No leukostasis was detected in the normal subjects, while it was detected in te diabetic patient. Flow cytometry revealed an increase in CD11b and a decrease in CD62L expression of leukocytes after labeling, suggesting that compared to normal leukocytes FLALs are more susceptible to interact with vascular endothelium. CONCLUSIONS: The use of FLAL is presently the only technique applicable in humans for study of leukocyte transit in the retina. Their preparation is technically simple and unexpensive. Precise measurement of the velocity of leukocytes in small vessels can be obtained. Despite evidence of a certain degree of leukocyte activation after the labeling procedure, no leukostasis was detected in vivo in normal subjects. Potential applications for this technique may include the detection of leukostasis in the human retina during severe forms of diabetes and retinal phlebitis.

Adult↗

Suppression of ocular inflammation in endotoxin-induced uveitis by inhibiting nonproteolytic activation of prorenin.

PURPOSE: A recent study revealed that angiotensin receptor signaling mediates ocular inflammation and neovascularization. It was also found that prorenin undergoes nonproteolytic activation leading to upregulation of the renin-angiotensin system (RAS) when prorenin receptor interacts specifically with the handle region of prorenin. The purpose of the present study was to elucidate the role of the receptor-dependent nonproteolytic activation of prorenin in ocular inflammation in endotoxin-induced uveitis (EIU). METHODS: EIU was induced in Long-Evans rats by a single intraperitoneal injection of 100 microg lipopolysaccharide (LPS). Tissue localization of total prorenin, prorenin receptor, and activated prorenin in the EIU retina was examined by immunohistochemistry. To inhibit the prorenin receptor-mediated upregulation of the RAS, a decoy handle-region peptide (HRP) was intraperitoneally administered 24 hours before and immediately after the injection of LPS. Twenty-four hours after LPS injection, leukocyte adhesion to the retinal vasculature was evaluated with a concanavalin A lectin perfusion-labeling technique. In addition, leukocyte infiltration into the vitreous cavity and protein concentration in the anterior chamber were also measured. Retinal mRNA and protein levels of intercellular adhesion molecule (ICAM)-1, interleukin (IL)-6, and C-C chemokine ligand (CCL) 2/monocyte chemotactic protein (MCP)-1 were examined by RT-PCR and ELISA. RESULTS: Retinal vessels in rats with EIU were strongly positive for total prorenin, prorenin receptor, and activated prorenin. Systemic treatment with HRP resulted in dose- and time-dependent inhibition of the leukocyte adhesion and infiltration and the protein leakage, all of which were increased by the induction of EIU. Retinal mRNA expression and protein levels of ICAM-1, CCL2/MCP-1 and IL-6, induced in rats with EIU, were also significantly suppressed with application of HRP. CONCLUSIONS: These findings demonstrate for the first time that nonproteolytically activated prorenin plays a significant role in the development of ocular inflammation in the EIU model. The present study suggests the potential use of HRP, a decoy peptide binding to the prorenin receptor, as a therapeutic agent to reduce ocular inflammation.

Animals↗

Relation between superficial capillaries and foveal structures in the human retina.

When examining semithin Epon sections of human retinas, it became evident that superficial capillaries showed four different positions, according to the thickness of the ganglion cell layer. For the clear view of the distribution of the position of superficial capillaries, the intrafoveal region was subdivided into four zones, based on the thickness of the ganglion cell layer; the foveola and the A-, B-, and C-zone. The foveola has no ganglion cell layer, and the A-zone has a ganglion cell layer thinner than 15 microns. These regions lack superficial capillaries. In the B-zone, the ganglion cell layer is 15-45 microns thick, and here the superficial capillaries lie in the outer boundary of the ganglion cell layer. The C-zone and parafovea have a ganglion cell layer thicker than 45 microns, and superficial capillaries are present within the ganglion cell layer. The perifovea has a ganglion cell layer 15-45 microns thick. In the temporal perifovea, where the nerve fiber layer is not so distinct, superficial capillaries are located on the outer boundary of the ganglion cell layer. In the other portion of the perifovea, superficial capillaries lie in the inner boundary of the ganglion cell layer. Out of the perifovea, where the ganglion cell layer is thinner than 15 microns, most of superficial capillaries touch both boundaries of the ganglion cell layer. Major retinal vessels touch the ganglion cell layer and lie in the similar position to that of superficial capillaries.

Adult↗

Talc retinopathy in primates. A model of ischemic retinopathy: I. Clinical studies.

Four rhesus monkeys received intravenous injections of talc twice weekly for 3 1/2 to ten months. Within one month, talc particles were visible in fine perifoveal retinal vessels in the posterior pole. Continued deposition of talc could then be seen after subsequent injections. Hemorrhages in the nerve fiber layer, cotton-wool patches, and whitish plaques in the choroid were visible ophthalmoscopically. Fluorescein angiography revealed precapillary arteriolar occlusions, capillary nonperfusion, an abnormal foveal avascular zone, and retinal vascular leakage. Vitreous fluorophotometric findings were abnormal in all five eyes tested, while electroretinograms were normal in two eyes with advanced talc retinopathy. Talc retinopathy in the primate is similar to ischemic retinopathies in humans, including human talc retinopathy, sickle cell retinopathy, and hypertensive retinopathy. Subsequent reports will describe the light microscopic and ultrastructural changes in these eyes using tracer studies with in these eyes using tracer studies with horseradish peroxidase.

Animals↗

Indocyanine green angiography anomalies in ocular syphilis.

OBJECTIVE: To report indocyanine green (ICG) angiography anomalies in ocular syphilis. DESIGN: A noncomparative, interventional case series. PARTICIPANTS: Eight patients (16 eyes) affected by ocular syphilis. METHODS: All patients presenting with a diagnosis of active ocular syphilis between January 1994 and December 2001 were evaluated by a standard fluorescein and ICG angiography protocol. ICG angiography was repeated after completion of systemic antitreponemal and antiinflammatory treatment. RESULTS: ICG angiography anomalies were detected in 12 (75%) of 16 eyes. Two types of anomalies were observed: late-phase scattered hyperfluorescent spots (11 eyes) and persistent staining of retinal vessels (1 eye). Of these 12 eyes, 4 had no alteration by concomitant fluorescein angiography. When ICG angiography was repeated (5 +/- 1 weeks after the beginning of treatment), ICG angiography anomalies disappeared. CONCLUSIONS: ICG angiography may be a valuable tool in the assessment of patients with active ocular syphilis. Retinal and choroidal vascular anomalies can be determined that would otherwise go undetected by funduscopy and/or fluorescein angiography. It can also be useful in monitoring antitreponemal therapy.

Anti-Bacterial Agents↗