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PubMed2007

VLA-4 blockade suppresses endotoxin-induced uveitis: in vivo evidence for functional integrin up-regulation.

Leukocyte adhesion to the vascular wall is a critical early step in the pathogenesis of inflammatory diseases and is mediated in part by the leukocyte integrin, VLA-4, which binds to endothelial vascular cell adhesion molecule (VCAM) -1. Here, we investigate VLA-4's role in endotoxin-induced uveitis (EIU). At various time points (6-48 h) after EIU induction, the severity of the inflammation was evaluated by quantifying cell and protein content in the aqueous fluid, firm leukocyte adhesion in the retinal vessels, and the number of extravasated leukocytes into the vitreous. Functional activation of VLA-4 in vivo was investigated in our previously introduced autoperfused micro flow chamber assay. Firm adhesion of EIU leukocytes to immobilized VCAM-1 under physiological blood flow conditions was significantly increased compared with normal controls (P<0.05), suggesting an important role for VLA-4 in EIU. VLA-4 blockade in vivo significantly suppressed all uveitis-related inflammatory parameters studied, decreasing the clinical score by 45% (P<0.01), protein content in the aqueous fluid by 21% (P<0.01), retinal leukostasis by 68% (P<0.01), and leukocyte accumulation in the vitreous by 75% (P<0.01). Our data provide novel evidence for functional up-regulation of VLA-4 during EIU and suggest VLA-4 blockade as a promising therapeutic strategy for treatment of acute inflammatory eye diseases.

Animals↗
PubMed2002

Upregulation of glucose-dependent insulinotropic polypeptide and its receptor in the retina of streptozotocin-induced diabetic rats.

The pathology of diabetic retinopathy includes dilatation and beading of retinal vessels, and vascular sheathing. To gain a better understanding of the molecular events leading to diabetic retinopathy, we investigated disease-specific gene responses by screening differential expression using cDNA microarray. Male Sprague-Dawley rats were intraperitoneally injected with streptozotocin (STZ, 50 mg/kg) or the control buffer and were maintained for 6 weeks. Total RNA extracted from the retinas of both groups was used for cDNA microarray analysis. Signals from all the spots representing hybridized DNA were quantified and compared between the normal and diabetic rat retinas. Among 1176 genes analyzed, the retinal expression of glucose-dependent insulinotropic polypeptide (GIP) was found to increase in STZ-induced diabetic rats compared to controls. GIP is a secreted protein, known to be released from the small intestine, which potentiates glucose-induced insulin secretion from the pancreas. However, the expression of GIP and its receptor (GIPR) has not been previously noted in the rat retina. To further validate the expression of GIP in the rat retina and to determine its possible role in the development of early diabetic retinopathy, we investigated its expression by RT-PCR, Northern blotting, and immunohistochemistry in normal and diabetic rat retinas. GIP mRNA and protein are not only expressed in the rat retina, but their levels are greater in the diabetic rat as compared to controls. And GIPR expression was also upregulated in the retinas of STZ-induced diabetic rats. We here demonstrate for the first time the expression of GIP and GIPR in the rat retina. And we also revealed some genetic events in the early stage of diabetic retinopathy including the de novo increment of GIP and GIPR expression in the retina.

Animals↗
PubMed1982

Changes in pO2 induce retinal autoregulation in vitro.

Vascular autoregulation maintains stable retinal function in vivo in the face of changes in arterial pO2. We observed autoregulatory changes in the flow of perfusate through the isolated cat eye in response to changes in pO2. Hydrostatic perfusion pressure and all other variables of the perfusate, except for pO2, were kept constant. Throughout the experiments the viability of the eye was monitored by electroretinography. In nine short periods of hypoxia, pO2 of the perfusate was reduced by 12%-42% compared to the control. In eight of these experiments the flow rate of the perfusate increased significantly. Retinal vasodilation during hypoxia was also documented by indocyanine green angiography, monitored by TV, and photographed. In seven periods of hyperoxia, pO2 was raised by 7%-38%. In all cases the flow of the perfusate decreased. These changes in flow are interpreted as resulting from autoregulative vasodilation and vasoconstriction of the retinal vessels. The b-wave of the ERG increased and decreased parallel with pO2 of the perfusate. This indicates that autoregulation in vitro does not sufficiently compensate for changes in pO2. This is in contrast to our findings from a previous study in the anesthetized cat.

Animals↗
PubMedDate not supplied

Crystalline retinopathy.

A 52-year-old Japanese woman had retinal crystalline deposits with atrophy of the pigment epithelium and choriocapillaris and pigment clumps in the periphery. The patient did not have corneal crystals. The crystals were seen biomicroscopically in all layers of the retina and on the retinal vessels. The diagnosis of crystalline retinopathy was made. The progressive nature of the disease was confirmed, based on a 9-year follow-up. The authors reviewed this condition in the Japanese literature and believe that crystalline retinopathy may not be as rare in the Orient as previously thought.

Asian People↗
PubMed1989

Diabetic retinopathy: a leading cause of new blindness.

Some of the basic underlying processes in the development of diabetic retinopathy include changes in the walls of retinal vessels, with occlusion and leakage. These result in edema, hemorrhage, hard exudates, plaques, and ischemia, leading to neovascularization. When proliferative retinopathy supervenes, it may result in complete blindness. Internists and family practice physicians should be alert for early signs of diabetic retinopathy. Ideally, diabetic patients should have their eyes examined yearly by an ophthalmologist. A fundus examination without dilation and usually without acuity testing rarely detects proliferative or early background retinopathy. Multicenter studies have shown that photocoagulation of new vessels with the argon laser may significantly reduce the incidence of severe visual loss. This treatment method has the potential of reducing the incidence of diabetic blindness by 60% to 80%. Photocoagulation is not a "cure" for diabetic macular edema; when used judiciously, however, it can sometimes further reduce visual loss caused by this common disease. The course of diabetic retinopathy in individual cases is unpredictable. After photocoagulation, some patients cannot see as well as before, though in others the progress of the disease is arrested. There is a conservative concern about a procedure that destroys retinal tissue in the hope of limiting the progression of the disorder. Yet photocoagulation appears to be the only alternative until a better treatment is developed through basic research.

Blindness↗
PubMed1981

Choroidal ischemia after extracapsular cataract extraction by phacoemulsification.

Three patients developed apparent choroidal ischemia after phacoemulsification. The outer half of the posterior retina appeared white after operation, with confluent lesions in the posterior pole and splotchy white areas in the midperiphery. The separate lesions appeared similar in pattern to the lobular division of the choriocapillaris, and the retinal vessels were not involved. The white lesions resolved in two to three weeks, leaving alterations in the pigment epithelium. Vision was transiently reduced in each eye but returned to a nearly normal level in two of three affected eyes, although paracentral scotomas persisted. In each case of phacoemulsification, the posterior lens capsule was either damaged or was removed. In all three cases, an investigational type of irrigating solution (BSS Plus) containing balanced salt, glutathione, and other constituents was used. Controlled ocular compression was performed before operation using a pneumatic device in two cases. However, the cause of retinal and choroidal damage now described was probably excessively elevated intraocular pressure during the operation.

Adult↗
PubMed1988

Combined hamartoma of the retina and retinal pigment epithelium of the juxtapapillary retina and optic disc.

An 11-year-old Japanese girl had a greenish-gray, slightly elevated lesion at the optic disc and juxtapapillary retina of the right eye that was diagnosed as a combined hamartoma of the retina and retinal pigment epithelium. A gliotic epiretinal membrane partially covered the lesion. Tortuous retinal vessels, which leaked fluorescein dye, were noted ophthalmoscopically. The lesion remained stable during a follow-up period of 1 year. After reviewing the Japanese literature, we concluded that the combined hamartoma may not be as rare in Japan as previously thought.

Child↗
PubMed1977

[On the treatment of acute arterial circulatory disturbances of the retina and optic nerve (author's transl)].

After discussing basic therapeutic principles for the treatment of acute arterial occlusions of the retina and N. opticus (fibrinolysis, anticoagulation, corticoids, vasoactive drugs) the problems in employment of vasodilating drugs and the necessity of concomitant administration of strophanthine or digitalisglycosides are outlined. Results obtained after the administration of 3,7-Dimethyl-1-(5-oxo-hexyl)-xanthine (Pentoxifylline, Trental) in the treatment of 49 cases suffering from occlusion of the retinal vessels and 23 cases with vascular occlusion in the N. opticus are reported and commented with a view to the bad prognosis of these serious disorders, 55% of the patients showing definite improvement of visual acuity. Therapeutic guidelines resulting from these experiences are presented.

Acute Disease↗
PubMed1995

Retinal distortion and cotton-wool spots associated with epiretinal membrane contraction.

PURPOSE AND BACKGROUND: Several articles on surgery for macular pucker have noted the presence of intraretinal white spots, presumably cotton-wool spots, associated with epiretinal membranes. It was proposed that membrane contraction and resultant nerve fiber layer distortion might lead to blockage of axoplasmic flow and thus a cotton-wool spot. To see whether the observations supported this concept, the authors studied patients with epiretinal membranes associated with intraretinal white spots involving the center of the fovea, where there are normally no retinal vessels and the only axons are in Henle fiber layer. METHODS: Four patients with epiretinal membranes associated with prominent areas of intraretinal whitening involving the center of the fovea were examined before and after surgery. Observations and measurements were made from projected fundus photographs. RESULTS: The intraretinal white spots, which appeared preoperatively to lie in the center of the fovea, proved to have been pulled in from more peripheral retina by the epiretinal membrane. These white areas were associated with surprisingly great distortion of the inner retina. Stretching of the inner retina seemed to play a larger role in the retinal distortion than full-thickness retinal folding. CONCLUSION: The appearance and time course of these intraretinal white lesions were consistent with cotton-wool spots caused by mechanical disruption of axonal flow. The marked retinal stretching and distortion of the innermost layers of the retina were the most striking findings in this study and also seemed consistent with the concept that membrane contraction and resultant nerve fiber layer distortion might lead to blockage of axoplasmic flow and thus a cotton-wool spot.

Axonal Transport↗
PubMed2006

The dipeptide Arg-Gln inhibits retinal neovascularization in the mouse model of oxygen-induced retinopathy.

PURPOSE: Premature infants undergoing intensive care are highly vulnerable to amino acid deprivation. Supplementation of glutamine or arginine has resulted in beneficial effects in human neonates. This study was conducted to examine the effect of the dipeptide arginyl-glutamine (Arg-Gln) on vascular endothelial cell growth factor (VEGF) levels in primary human retinal pigment epithelial (hRPE) cell cultures and on inhibition of neovascularization in the oxygen-induced retinopathy (OIR) model. METHODS: The effects of Arg-Gln on VEGF levels were measured in supernates from hRPE cells by using ELISAs. For in vivo studies, mouse pups received twice-daily intraperitoneal injections of Arg-Gln, a control dipeptide (Ala-Gly) or were not injected. Retinal flatmounts from one cohort were prepared and retinal vessel morphology examined. The contralateral eyes were embedded, sectioned, and stained to count preretinal neovascular nuclei. RNA was isolated from retinas of selected animals and was used to quantify VEGF mRNA by real-time RT-PCR. RESULTS: Treatment of hRPE cells with Arg-Gln decreased VEGF levels in a dose-dependent manner. In the OIR model, Arg-Gln at 5 g/kg per day reduced preretinal neovascularization by 82%+/-7% (P<0.005), when compared with the control dipeptide Ala-Gly, and reduced VEGF mRNA by 64%+/-9% (P<0.001). CONCLUSIONS: Arg-Gln dramatically inhibited retinal neovascularization in the OIR model. This effect was associated with a reduction in retinal VEGF mRNA levels. Similarly the dipeptide reduced VEGF expression in hRPE cells, a cell type likely to respond to retinal hypoxia by expressing VEGF. Arg-Gln appears to be safe and, with future studies in human infants, may prove beneficial in the prevention of ROP.

Angiogenesis Inhibitors↗
PubMed1998

Fluid blood level in cystoid space resulting from central retinal vein occlusion.

BACKGROUND: A hemorrhagic and cystoid maculopathy developed in a patient with a central retinal vein occlusion. There was an unusual finding of a fluid blood level in the inferior region of the central large cystoid space. This clinical finding has been associated with cystoid macular edema after aphakic/pseudophakic cataract surgery. METHOD: A case report is presented and a review of the literature was conducted to determine the frequency of this condition and gain knowledge of the possibility of the pathophysiology. RESULTS: This is only the second case reported in the literature of a fluid blood level seen in a patient with obstructive venous retinopathy. The pathophysiology is likely to be the transitory bleeding of a retinal vessel into the cystoid space. CONCLUSION: The finding of a fluid blood level in a patient with a BRVO or CRVO is a rare event. Since this condition has not been associated with diabetic hemorrhagic retinopathy, any diabetic patient displaying such a clinical finding should be suspected of having obstructive venous disease.

Follow-Up Studies↗
PubMed1998

Renal pathology patterns in type II diabetes mellitus: relationship with retinopathy. The Collaborative Study Group.

BACKGROUND: The glomerular and retinal vessels are both affected in patients with type I and type II diabetes mellitus. However, the prevalence of the nodular form of diabetic glomerular sclerosis (Kimmelstiel Wilson lesion) and other forms of glomerular pathology including diffuse mesangial sclerosis and their clinical correlates in type II diabetes are less well known. In addition, although recent studies have suggested that non-diabetic glomerular disease was a common cause of proteinuria in type II diabetes, the prevalence of other diseases is unknown. The literature on this subject is clouded by clinical bias regarding patients with diabetes who undergo renal biopsy. METHODS: Glomerular and retinal pathology and clinical correlates were studied in 36 patients enrolled in a prospective clinical trial of patients with type II diabetes mellitus, proteinuria, renal insufficiency, and hypertension. RESULTS: Seventeen biopsies had diabetic glomerular sclerosis with Kimmelstiel Wilson nodules; 15 biopsies had glomerular changes characteristic of the diabetic state including enlarged glomeruli and an increase in mesangial matrix without Kimmelstiel Wilson nodules (mesangial sclerosis lesion); and two had other primary glomerular diseases (IgA and membranous nephropathy). Patients with Kimmelstiel-Wilson nodules had elevated serum creatinines compared to patients with mesangial sclerosis lesions, but there were no other significant differences. Patients with Kimmelstiel Wilson nodules had more severe overall retinopathy than those with mesangial sclerosis lesions (P = 0.0043): six of seven with proliferative retinopathy had Kimmelstiel Wilson nodules, and seven of the eight patients without retinopathy had mesangial sclerosis lesions. CONCLUSIONS: The two discrete patterns of glomerular pathology and the correlation between diabetic retinopathy and the Kimmelstiel-Wilson lesion but not the mesangial sclerosis lesion suggest that the Kimmelstiel Wilson and mesangial sclerosis lesions of diabetic glomerulosclerosis are caused by different pathogenetic mechanisms. In this study, diabetic glomerulosclerosis was responsible for the clinical renal abnormalities in 94%, of patients with type II diabetes mellitus.

Adult↗
PubMed2004

Flicker observation light induces diameter response in retinal arterioles: a clinical methodological study.

AIM: To investigate diameter changes in retinal arterioles in response to flicker variations of the examination light. METHODS: One randomised eye of five healthy subjects (mean age 33.8 (SD 1.6) years) was examined. The arterial diameter response to flicker light (12.5 Hz, 530-600 nm, duration 20 seconds) was automatically and continuously measured online three times by retinal vessel analyser (RVA) and once offline from flash images using the VesselMap program. RESULTS: An arterial diameter response to flicker light was found both by RVA and by analysis of flash images (p<0.001). The maximum induced dilation reached at the end of the flicker period was +7.4% (SD 2.4%) in the RVA measurements and +3.5% (0.8%) in the photographs (p = 0.01). In both techniques the vascular diameter overshot the baseline approximately 10 seconds. In the RVA measurements a minimum of -4.6% (1.9%) (p = 0.01) was measured 22 (4.7) seconds after the end of flicker exposure. CONCLUSION: Flicker evoked response for retinal arterioles was found both by RVA and by analysis of flash images. The authors believe that the method is suitable for the quantitative investigation of retinal vasosclerosis, especially in association with arteriosclerotic and hypertensive systemic disease.

Adult↗
PubMed2006

Multiple retinal hemorrhage following anterior chamber paracentesis in uveitic glaucoma.

PURPOSE: We describe the occurrence of a massive retinal hemorrhage following anterior chamber paracentesis in uveitic glaucoma. METHODS: A 33-year-old man who suffered from uveitic glaucoma was transferred to our hospital. The lOP in both his eyes was documented to vary between 11 mmHg and 43 mmHg and remained at a continuously high level for 7 months despite maximally tolerable medical treatment. A paracentesis was performed bilaterally to lower the IOP. RESULTS: Immediately after the paracentesis, massive retinal hemorrhages occurred in the left eye. Multiple round blot retinal hemorrhages with white centers occurred in the equator and peripheral retina, and small slit hemorrhages were observed in the peripapillary area. A fluorescence angiography(FAG) showed no obstruction of retinal vessels but a slightly delayed arteriovenous time in the left eye. CONCLUSIONS: It is important to be aware that patients who have a persistent relatively high IOP are at an increased risk of developing decompression retinopathy due to paracentesis and filtering surgery.

Adult↗
PubMedDate not supplied

Retinal fluorescein angiographic evidence for atheromatous microembolism. Demonstration of ophthalmoscopically occult emboli and post-embolic endothelial damage after attacks of amaurosis fugax.

There is evidence that microemboli responsible for amaurosis fugax may be atheromatous but it can elude ophthalmoscopic confirmation, because such emboli quickly fragment and disappear from view in the retinal vessels. This report documents 2 patients in whom fluorescein angiography of the retina provided evidence of microembolization after an attack of amaurosis although the fundus appeared normal. In one patient the angiogram revealed intraluminal material; in the other it showed fluorescein leakage from patent arteriolar bifurcations.

Aged↗
PubMed2003

Selective occlusion of subfoveal choroidal neovascularization in angioid streaks by using a new technique of ingrowth site treatment.

PURPOSE: To evaluate the visual and angiographic effects, as well as optical coherence tomography (OCT) findings, after a new treatment-neovascular ingrowth-site photothrombosis-in patients with subfoveal choroidal neovascularization (CNV) secondary to angioid streaks. DESIGN: Prospective noncomparative small case series. PARTICIPANTS: Five eyes of 5 patients with angioid streaks in whom fluorescein and conventional indocyanine green (ICG) angiography clearly demonstrated distinct CNV vessels supplying the subfoveal neovascular complex. INTERVENTION: All five eyes were submitted to ICG-mediated photothrombosis of the neovascular ingrowth site. This novel, laser/dye-mediated technique uses large-spot, lower-intensity 810-nm light for continuous application of laser energy to ICG concentrated in vascular lesions. MAIN OUTCOME MEASURES: Visual outcome and the results of fluorescein angiography, ICG angiography, and OCT evaluation. RESULTS: Fluorescein and conventional ICG angiography were sufficient to identify the CNV ingrowth site, which was juxtafoveal in 2 and extrafoveal in 3 of the 5 eyes in this series. Obliteration of the entire neovascular lesion was achieved in all patients within the first hour after ICG-mediated photothrombosis of the CNV ingrowth site. At 1 week, the mean change in best-corrected visual acuity from baseline was +3.2 (+/-1.4) lines. Twelve months after treatment, visual acuity improved by 3 or more lines in all patients, and decreased leakage of fluorescein from the CNV, as well as OCT evidence of reduced or resolved retinal edema, was seen at the last follow-up visit. Major complications, such as immediate severe visual loss and retinal vessel occlusion in the early posttreatment period, were not identified in the 5 patients submitted to the procedure. CONCLUSIONS: Photothrombosis of the CNV ingrowth site by using lower-intensity light to direct laser energy continuously after IV ICG infusion is a safe and effective technique for rapid induction of CNV hypoperfusion in selected patients and is associated with considerable improvement in visual acuity and partial restoration of the retinal architecture up to 12 months after treatment.

Aged↗
PubMed2006

Histopathologic findings after radial optic neurotomy in central retinal vein occlusion.

PURPOSE: Radial optic neurotomy (RON) in central retinal vein occlusion (CRVO) is a novel strategy that is aimed at relief of mechanical pressure on the central retinal vein. We report on histopathologic findings in a human eye 18 weeks after RON. DESIGN: Interventional case report. METHODS: Eighteen weeks after RON for ischemic CRVO, an eye was enucleated because of neovascular glaucoma and examined histologically. RESULTS: Histopathologic evidence demonstrated displaced fragments of Bruch's membrane surrounded by retinal tissue at the nasal side of the papilla. A discrete scar was noted at this site that reached the cribriform plate without involving the adjacent sclera or the retinal vessels. The optic nerve showed advanced atrophy with a small temporal sector of viable nerve fibers. CONCLUSIONS: Histopathologic findings after RON do not provide evidence for the postulated mechanism of action. It appears prudent to further evaluate this technique before its general implementation in the management of CRVO.

Aged↗
PubMed1982

Experimental central serous chorioretinopathy in monkey eyes: fluorescein angiographic findings.

In an adult Japanese monkey (Macaca fuscatus), intravenous injections of adrenalin were repeated daily: 0.125 mg/kg for 7 days and 0.375 mg/kg from the 11th day on. In a cynomolgus monkey (Macaca irus), daily injections were carried out with intravenous adrenalin (0.11 mg/kg for 12 days and a double dose from the 13th day on) and also with intramuscular prednisolone. After the 39th injection in the former and after the 32nd injection in the latter monkey, disciform serous retinal detachment was seen to occur in the posterior pole region, and fluorescein angiography revealed multiple dye leakage spots at the level of the retinal pigment epithelium. Sometimes these changes subsided, but on continuing injections, these changes recurred on new locations. Two types of fluorescein leakage spots were recognized, i.e. ink blot type with progressive simple enlargement with time and the mushroom or jet type showing these patterns during enlargement. No abnormality was found in the optic disc, retinal vessels or in the choroidal circulation. The fluorescein angiographic findings were in close resemblance with those seen in the human central serous chorioretinopathy. It was discussed that these fundus changes of the monkey eye produced by repeated adrenalin injections would serve as a good animal model of the human disease.

Animals↗