endothelin-1 and Retinal-Vein-Occlusion

Retinal vein occlusion (RVO) is a common vascular disease of retina; however, the pathomechanism leading to RVO is not yet clear. In general, increasing age, hypertension, arteriosclerosis, diabetes mellitus, dyslipidemia, cardiovascular disorder, and cerebral stroke are systemic risk factors of RVO. However, RVO often occur in the unilateral eye and sometimes develop in young subjects who have no arteriosclerosis. In addition, RVO show different variations on the degrees of severity; some RVO are resolved without any treatment and others develop vision-threatening complications such as macular edema, combined retinal artery occlusion, vitreous hemorrhage, and glaucoma. Clinical conditions leading to RVO are still open to question. In this review, we discuss how to treat RVO in practice by presenting some RVO cases. We also deliver possible pathomechanisms of RVO through our clinical experience and animal experiments.

Topics: Animals; Arteriosclerosis; Diabetes Complications; Dyslipidemias; Endothelin-1; Humans; Hypertension; Retina; Retinal Vein Occlusion; Risk Factors; Stroke; Veins

Retinal vein occlusion (RVO) risk factors largely coincide with cardiovascular risk factors. Endothelin-1 (ET-1), the most potent vasoconstrictor with proinflammatory properties, is a known cardiovascular risk factor. In this study, we explore the role of serum ET-1 as a potential risk factor for RVO.. Endothelin-1 serum levels were measured in patients with RVO and control subjects. Samples were measured using the sandwich enzyme-linked immunosorbent assay for the quantitative determination of human big endothelin-1 (Biomedica Group, Austria).. The study consisted of 147 RVO patients and 150 control subjects. Median serum ET-1 was significantly higher in RVO patients (0.26 pmol/L; range, 0.19-0.37 pmol/L) compared with control subjects (0.10 pmol/L; range, 0.05-0.22 pmol/L) (P < 0.0001) independent of the occlusion site. The difference remained significant after adjusting for arterial hypertension, diabetes mellitus, history of stroke, history of myocardial infarction, history of venous thromboembolism, glomerular filtration rate, and c-reactive protein.. In conclusion, our results suggest that ET-1 is a potential risk factor for all types of RVO.

Topics: Endothelin-1; Humans; Hypertension; Retinal Vein Occlusion; Risk Factors; Stroke

To investigate aqueous humor concentrations of endothelin-1 (ET-1) in patients with central retinal vein occlusion (CRVO) compared with patients with branch retinal vein occlusion (BRVO) and a normal control group.. A total 80 subjects were included in this prospective study, including 15 patients with CRVO, 20 patients with BRVO, and 45 patients who underwent cataract surgery and had no concomitant ocular disease. Aqueous humor levels of ET-1 were obtained before intravitreal bevacizumab injection (IVB) and after 1 month.. At baseline, the mean aqueous ET-1 level was 12.7±3.6 pg/mL in the CRVO group, 8.0±2.3 pg/mL in the BRVO group, and 2.0±0.9 pg/mL in the control group (P<0.001). After IVB, the mean aqueous level of ET-1 was 3.4±1.9 pg/mL (0.5-6.9 pg/mL) in the CRVO group and 1.8±1.0 pg/mL (0.3-3.2 pg/mL) in the BRVO group (P = 0.008). The mean aqueous ET-1 level was significantly reduced in both the patients with CRVO and those with BRVO (P<0.001).. The mean aqueous humor ET-1 level was significant higher in the patients with CRVO than those with BRVO and in the control group. After IVB, the mean level was significantly reduced in both the patients with CRVO and those with BRVO.

Topics: Aged; Bevacizumab; Endothelin-1; Female; Humans; Macular Edema; Male; Middle Aged; Prospective Studies; Retinal Vein Occlusion; Visual Acuity

Whilst the pathogenesis of retinal vein occlusion (RVO) is still unclear, systemic hypertension and increased level of endothelin-1 (ET-1) are known risk factors. Therefore, we studied the influence of ET-1 on the retinal veins in hypertensive rats.. We focused on the behavior of retinal veins in spontaneous hypertensive rats (SHR). To determine whether ET-1 was associated with the blood flow in eyes of SHRs, the chorioretinal blood flow in the rats was assessed using laser speckle flowgraphy (LSFG-Micro, Softcare, Fukuoka, Japan) before and after an intravenous injection of ET-1 under general anesthesia. In addition, retinas from SHRs and age-matched normotensive Wistar-Kyoto rats (WKYs) were removed, and retinal sections were immunostained for the ET-A and ET-B receptors. The protein levels of both ET-1 receptors and hypoxia-inducible factor 1 (HIF-1) in the retinal tissues were also determined by western blot analysis.. One of the retinal veins became exceptionally constricted and was nearly occluded, and the chorioretinal blood flow significantly decreased in the retinas of SHRs following the injection of ET-1. Immunoreactivity to ET-A receptor was higher in SHR retinas than in WKY retinas. The protein levels of ET-A receptor and HIF-1 were also significantly higher in SHR retinas than in WKY retinas.. An increase of ET-1 in circulating blood leads to the local constriction of retinal veins and this effect is accentuated in hypertensive rats by an upregulation of ET-A receptor. It is plausible that such a constriction of retinal veins increases retinal venous pressure, and may even contribute to the pathogenesis of RVO.

Topics: Animals; Choroid; Endothelin-1; Hypoxia-Inducible Factor 1, alpha Subunit; Injections, Intravenous; Laser-Doppler Flowmetry; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Endothelin A; Receptor, Endothelin B; Regional Blood Flow; Retinal Vein; Retinal Vein Occlusion; Retinal Vessels; Vasoconstriction

To evaluate aqueous levels of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) in patients with branch retinal vein occlusion (BRVO) with and without normal tension glaucoma (NTG), and to assess the therapeutic efficacy of intravitreal bevacizumab (IVB) in these patients.. Sixteen eyes with NTG of 48 age and sex-matched eyes without NTG that had previously received IVB for BRVO were followed for 6 months. Aqueous VEGF and ET-1 levels were measured by enzyme-linked immunosorbent assay at the time of baseline IVB. Logarithm of the minimum angle of resolution best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at baseline and then at 1, 3, and 6 months postinjection.. The obstruction site of BRVO was closer to the optic disk in eyes with NTG compared with controls (P=0.001). Baseline BCVA, CMT, and VEGF levels were similar between the 2 groups. Baseline ET-1 levels were significantly higher in eyes with NTG than those without NTG (P=0.009). After IVB, there was a significant improvement in both BCVA and CMT at 6 months, irrespective of the presence of NTG. However, BCVA in the presence of NTG was significantly worse at 6 months compared with eyes without NTG even though CMT was similarly reduced in both groups (P=0.04).. Aqueous VEGF levels are similar in patients with BRVO with or without NTG, whereas aqueous ET-1 levels are elevated in the presence of NTG. Although IVB may be effective in the treatment of BRVO, the presence of NTG may limit visual recovery despite anatomic recovery of CMT.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Aqueous Humor; Bevacizumab; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intraocular Pressure; Intravitreal Injections; Low Tension Glaucoma; Macular Edema; Male; Middle Aged; Retinal Vein Occlusion; Vascular Endothelial Growth Factor A; Visual Acuity

Purpose. To investigate the effect of the endothelin(A) receptor inhibitor BQ-123 on the retinal arteriolar vasculature in minipig retinas in normal eyes and eyes with acute branch retinal vein occlusion (BRVO). Methods. Seven healthy eyes of seven minipigs and six eyes of six minipigs with experimental BRVO were evaluated under systemic anesthesia. An intravitreal juxta-arteriolar microinjection of 30 microL BQ-123 0.61 microg/mL (pH 7.4) was performed in all but one eye from each group, into which the physiologic saline vehicle alone was injected. Vessel-diameter changes were measured with a retinal vessel analyzer. Results. In healthy minipig retinas (n = 6), arteriolar diameter (+/-SD) increased 6.19% +/- 3.55% (P < 0.05), 25.98% +/- 2.37% (P < 0.001), 23.65% +/- 1.2% (P < 0.001), and 16.84% +/- 1.95% (P < 0.001), at 1, 5, 10, and 15 minutes, respectively, after BQ-123 microinjection. Two hours after experimental BRVO (n = 5), the retinal arteriolar diameter had decreased (13.07% +/- 5.7%; P < 0.01). One, 5, 10, and 15 minutes after BQ-123 microinjection, retinal arteriolar diameter had increased by 7.14% +/- 3.3% (P < 0.01), 26.74% +/- 7.63% (P < 0.001), 23.67% +/- 6.4% (P < 0.001), and 16.09% +/- 3.41% (P < 0.001), respectively. Vehicle only injection had no vasoactive effect on physiologic or BRVO retinas. Conclusions. A significant increase in retinal arteriolar diameter was demonstrated after juxta-arteriolar BQ-123 microinjection in healthy and in acute BRVO minipig retinas. The results suggest a role for endothelin-1 in maintaining retinal basal arteriolar tone. Reversing the BRVO-related vasoconstriction by juxta-arteriolar BQ-123 microinjection could bring a new perspective to the management of BRVO.

Topics: Acute Disease; Animals; Arterioles; Disease Models, Animal; Endothelin A Receptor Antagonists; Endothelin-1; Microinjections; Muscle, Smooth, Vascular; Peptides, Cyclic; Retinal Artery; Retinal Vein Occlusion; Swine; Swine, Miniature; Vasodilation

Vascular occlusive diseases are usually seen in the elderly but can occur even in younger patients without arteriosclerosis. We assume a vascular dysregulation as a underlying pathogenetic mechanism.. In a prospective study we analysed the clinical findings of six patients under 55 years of age, three men with retinal vein occlusions and three women with branch retinal arterial obstructions. They were examined for signs of a vascular dysregulation and the endothelin-1 (ET-1) plasma level was measured.. In all patients the ET-1 plasma level was markedly elevated. The mean value (3.72 +/- 0.8 pg/ml) was significantly increased compared to normal values for that age (1.52 +/- 0.24 pg/ml; p < 0.001). In all cases an increased tendency for vascular dysregulation could be demonstrated in nailfold capillaroscopy. Furthermore, frequent coldness of the extremities was mentioned by every patient and migraine was mentioned by four patients whereas neither changes of the vessels in carotis and ophthalmica region nor disturbances in the haemostasis and fibrinolysis could be found.. All six patients with vascular occlusive diseases occurring before the age of 55 had a vascular dysregulation and increased ET-1 plasma levels. A relationship between the vascular dysregulation and the vascular occlusive diseases is therefore likely.

Topics: Acute Disease; Adult; Endothelin-1; Endothelium, Vascular; Female; Homeostasis; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Retinal Artery Occlusion; Retinal Vein Occlusion; Risk Factors; Skin Temperature; Vascular Resistance

Topics: Biomarkers; Endothelin-1; Humans; Retinal Vein Occlusion

To investigate whether plasma levels of endothelin-1 (ET-1), a potent vasoconstricting peptide that is crucial in regulating retinal blood flow, were elevated in patients with retinal vein occlusion (RVO).. ET-1 plasma concentrations were determined by radioimmunoassays in a double blind fashion in a group of 18 selected patients with RVO, in 20 healthy age matched non-smoking, normoglycaemic, normotensive control subjects, and in 15 patients with uncomplicated essential hypertension in the same age range.. Patients with RVO had significantly increased ET-1 plasma levels (14.22 (SD 4.6) pg/ml) compared with both normal subjects (7.90 (1.6) pg/ml; p < 0.05) and hypertensive patients (8.50 (2.9) pg/ml; p < 0.05). The highest concentrations of circulating ET-1 were found in patients with RVO of the ischaemic type (16.97 (3.5) pg/ml; p < 0.01; n = 7). Systemic hypertension alone did not account for the observed increase in plasma ET-1 concentrations.. These findings raise the possibility that the increased circulating ET-1 levels in patients with RVO may be a marker of the occlusive event, thereby suggesting that ET-1 homeostasis may be relevant to RVO pathogenesis and retinal ischaemic manifestations.

Topics: Adult; Aged; Biomarkers; Double-Blind Method; Endothelin-1; Female; Humans; Hypertension; Ischemia; Male; Middle Aged; Ocular Hypertension; Retinal Vein Occlusion; Retinal Vessels