losartan-potassium and Retinal-Detachment

To explore factors related to pathogenesis of rhegmatogenous retinal detachment (RRD) and development of proliferative vitreoretinopathy (PVR), vitreous levels of angiopoietin-1 and -2 (Ang-1 and -2), previously undefined in RRD, transforming growth factor-(TGF) β1, vascular endothelial growth factor (VEGF), erythropoietin (EPO) and proteolytic mediators of extracellular matrix remodelling (MMP-2 and -9) were compared in eyes with RRD and eyes with idiopathic macular hole or pucker.. Vitreous samples were collected from 117 eyes with RRD (study group) and 40 eyes with macular hole or pucker (control group). Growth factors were measured by ELISA and matrix metalloproteinases (MMPs) by gelatin zymography.. The mean vitreous concentrations of Ang-2, MMP-2, and MMP-9 were higher (all p < 0.01), whereas concentration of VEGF was lower (p = 0.01) in eyes with RRD relative to controls. Logistic regression analysis identified Ang-2 concentration as a novel marker of RRD (p = 0.0001, OR 48.7). Ang-1, EPO, and total TGF-β1 levels were not significantly different between the groups. However, TGF-β1 and MMP-2 were increased in eyes with total RRD compared to those with local RRD (p ≤ 0.05). In eyes with PVR, no differences were observed in any studied marker as compared with non-PVR eyes.. Current results reveal Ang-2 as a key factor upregulated in RRD. It may co-operate with fibrosis-associated factors and contribute to vascular complications such as breakdown of blood-eye barrier and PVR development.

Topics: Aged; Angiopoietin-1; Angiopoietin-2; Biomarkers; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Humans; Male; Matrix Metalloproteinases; Middle Aged; Prospective Studies; Retinal Detachment; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A; Vitreous Body

To elucidate the safety and efficacy of exogenous erythropoietin (EPO) for the protection of photoreceptor cells in a rat model of retinal detachment (RD).. Recombinant rat EPO (400 ng) was injected into the vitreous cavity of normal rats to observe the eye manifestations. Retinal function was assessed by flash electroretinograms. Histopathological examination of retinal tissue was performed at 14 days and 2 months after injection, respectively. To investigate the inhibitory effect of EPO on photoreceptor cell apoptosis in RD rats, 100, 200, or 400 ng EPO was injected into the vitreous cavity immediately after RD model establishment. Apoptosis of photoreceptor cells was determined at 3 days after injection. Caspase-3 activation was measured by western blot analysis and immunofluorescence, respectively, and the level of Bcl-X(L) expression was analyzed by western blot.. Intravitreal injection of EPO 400 ng into normal rats had no significant impact on retinal function, morphology, or structure. Apoptosis of retinal photoreceptor cells apparently increased after RD and was significantly reduced following EPO treatment. The thickness of the outer nuclear layer in the RD + 400 ng group was significantly thicker than that in other experimental RD groups both at 14 days and at 2 months after RD (P < 0.05). Western blot and immunofluorescence analyses showed decreased caspase-3 activation and increased Bcl-X(L) expression following EPO treatment.. Intravitreal injection of EPO 400 ng is safe, and EPO may suppress caspase-3 activation and enhance Bcl-X(L) expression, resulting in inhibition of apoptosis and protection of photoreceptor cells.

Topics: Animals; Apoptosis; bcl-X Protein; Blotting, Western; Caspase 3; Disease Models, Animal; Enzyme Activation; Erythropoietin; Fluorescent Antibody Technique; Intravitreal Injections; Male; Photoreceptor Cells, Vertebrate; Rats; Rats, Sprague-Dawley; Retinal Detachment

The aim of this study was to investigate the effects of supplemental erythropoietin (EPO) on its receptor (EPOR) and signal transduction pathways in rat model of retinal detachment (RD).. To investigate the effect of EPO on EPOR expression in RD rats 100, 200 or 400 ng EPO was injected into the vitreous cavity immediately after RD model was induced. Western blot and immunohistochemistry analyses were performed to measure EPOR expression. To investigate the effect of EPO on signal transduction pathways in RD rats single dose of 400 ng EPO was injected into the vitreous cavity immediately after RD model was induced. The total and phosphorylated levels of JAK2, Akt, ERK-1/2, STAT5 and NF-κB were assessed by western blot.. Western blot analysis showed that, compared with the normal control group, EPOR expression in the neurosensory retina was significantly increased in experimental RD groups (P < 0.05), but the differences were not significant between experimental RD groups (P > 0.05). Immunohistochemical examination indicated that EPOR staining on retinas became strongly positive 3 days after RD, with no significant difference in staining intensities between the treatment groups. Phosphorylated levels of JAK2, Akt, ERK-1/2, STAT5, and NF-κB were enhanced 3 days after RD, but only JAK2, Akt, and ERK-1/2 phosphorylation was further enhanced by 400 ng EPO treatment (P < 0.05).. Supplementary EPO cannot affect EPOR expression in detached retina, but EPO may activate both PI-3K/Akt and MAPK/ERK-1/2 signal transduction pathways in RD model.

Topics: Animals; Blotting, Western; Disease Models, Animal; Erythropoietin; Immunohistochemistry; Intravitreal Injections; Janus Kinase 2; Male; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-kappa B; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; Retinal Detachment; Signal Transduction; STAT5 Transcription Factor; Up-Regulation

Our purpose was to determine the vitreous erythropoietin (EPO) level in patients with rhegmatogenous retinal detachment (RRD) and proliferative vitreoretinopathy (PVR).. The levels of EPO in vitreous were measured using a sandwich enzyme-linked immunosorbent assay kit from 64 patients, of whom 40 had RRD, 13 had PVR and 11 had idiopathic macular hole as control.. The mean levels of EPO in the RRD group (54.6 +/- 7.3 mU/ml) and PVR group (104.1 +/- 20.8 mU/ml) were significantly higher than that in the idiopathic macular hole control group (14.4 +/- 3.6 mU/ml; p < 0.001, p = 0.003, respectively). The mean EPO level in PVR was higher than that in RRD, but the difference was not significant (p = 0.112).. The vitreous EPO level was upregulated in eyes with RRD and PVR.

Topics: Aged; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Humans; Middle Aged; Retinal Detachment; Retinal Perforations; Vitreoretinopathy, Proliferative; Vitreous Body

Erythropoietin (EPO), known for its role in erythroid cell differentiation, has been suggested to have a neuroprotective effect on retinal neurons. The aim of the current study was to investigate the expression pattern of EPO and erythropoietin receptor (EPOR) in the detached retina of a rat model of retinal detachment (RD).. Forty-eight albino Sprague-Dawley rats were randomized into normal control group (n = 6) and RD model group (n = 42). The rat RD model was established by slow injection of 1.4% sodium hyaluronate into the upper half of the subretinal space, in which the upper half of the neurosensory retina was detached from the underlying retinal pigment epithelium (RPE). The expression of EPO and EPOR mRNA/protein was determined at 1, 3, 6, 12, 24, 48, and 72 hr after sodium hyaluronate injection by semiquantitative RT-PCR and Western blot analysis, respectively. Meanwhile, the distributions of EPO and EPOR were examined by immunohistochemistry.. EPO and EPOR mRNA levels increased gradually after sodium hyaluronate injection and peaked 48 hr later. EPO mRNA level became significantly higher than that in the normal control group at 12 hr after injection, and EPOR mRNA level became significantly higher at 6 hr (p < 0.05). Moreover, the protein levels of EPO and EPOR presented a similar tendency to the mRNA level and became significantly higher than those in normal control group at 3 hr after injection (p < 0.05). Immunohistochemical results showed that both EPO and EPOR were strongly expressed all over the neurosensory retina 48 hr after injection, but EPOR was not found in the rod outer segment. Only weak expression of EPO and EPOR was noticed in the retina of normal control group.. The levels of EPO and EPOR in detached retina increase with the duration of retinal detachment and reach their peaks at 48 hr; most layers of detached neurosensory retina can express EPO and EPOR. It is indicated that the EPO/EPOR system might play an important role in protection of retinal neurons during RD; supplementation with exogenous EPO might promote the survival of retinal neurons.

Topics: Animals; Blotting, Western; Erythropoietin; Hyaluronic Acid; Immunohistochemistry; Injections; Male; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; Retina; Retinal Detachment; RNA, Messenger; Time Factors; Tissue Distribution

The aim of the current study was to measure the concentrations of erythropoietin in the vitreous fluid and analyze its association with vascular endothelial growth factor (VEGF) in ischemic vitreoretinal diseases. Vitreous fluid samples were collected from patients with proliferative diabetic retinopathy, branch retinal vein occlusion and idiopathic macular hole. Concentrations of erythropoietin and VEGF in vitreous fluid were significantly elevated in patients with proliferative diabetic retinopathy and branch retinal vein occlusion as compared to patients with macular hole. There were no differences in serum concentrations of erythropoietin and VEGF among patient groups. There was significant correlation between erythropoietin and VEGF concentrations in vitreous fluid. Erythropoietin was up-regulated in ischemic disorders and may act as an endogenous neuroprotective factor against ischemic retinal disorders.

Topics: Aged; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Humans; Ischemia; Male; Middle Aged; Retinal Detachment; Retinal Diseases; Vascular Endothelial Growth Factors; Vitreous Body

Topics: Adult; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Recombinant Proteins; Retinal Detachment; Retinal Neovascularization; Retinitis Pigmentosa