共查询到20条相似文献,搜索用时 0 毫秒
1.
Saurabh Luthra Ashish Sharma Joyce Dong Aneesh Neekhra Ana L Gramajo Gail M Seigel M Cristina Kenney Baruch D Kuppermann 《Indian journal of ophthalmology》2013,61(12):705-710
Purpose:
To evaluate the effect of bevacizumab on the mitochondrial function of human retinal pigment epithelial (ARPE-19), rat neurosensory retinal (R28) and human microvascular endothelial (HMVEC) cells in culture.Materials and Methods:
ARPE-19 and R28 cells were treated with 0.125, 0.25, 0.50 and 1 mg/ml of bevacizumab. The HMVEC cultures were treated with 0.125, 0.25, 0.50 and 1 mg/ml of bevacizumab or 1 mg/ml of immunoglobulin G (control). Mitochondrial function assessed by mitochondrial dehydrogenase activity (MDA) was determined using the WST-1 assay.Results:
Bevacizumab doses of 0.125 to 1 mg/ml for 5 days did not significantly affect the MDA of ARPE-19 cells. Bevacizumab treatment at 0.125 and 0.25 mg/ml (clinical dose) did not significantly affect the MDA of R28 cells; however, 0.50 and 1 mg/ml doses significantly reduced the R28 cell mitochondrial function. All doses of bevacizumab significantly reduced the MDA of proliferating and non-proliferating HMVEC.Conclusion:
Bevacizumab exposure for 5 days was safe at clinical doses in both ARPE-19 and R28 retinal neurosensory cells in culture. By contrast, bevacizumab exposure at all doses show a significant dose-dependent decrease in mitochondrial activity in both the proliferating and non-proliferating HMVEC in vitro. This suggests a selective action of bevacizumab on endothelial cells at clinical doses. 相似文献2.
Central retinal artery occlusion following orbital tumor resection: Is rapid intervention effective?
Mohammad Taher Rajabi Mohammad Naderan Seyed Ziaeddin Tabatabaei Mohammadi Mohammad Bagher Rajabi 《Indian journal of ophthalmology》2015,63(8):678-680
A 52-year-old male patient presented at our hospital with unilateral proptosis and vision loss in his left eye. Imaging evaluations showed orbital tumor, so the patient underwent surgery. About an hour later after tumor removal, patient developed sudden vision loss and became no light perception. Fundus evaluation revealed central retinal artery occlusion (CRAO). The patient was treated immediately with ocular massage and anterior chamber paracentesis as well as systemic therapy with mannitol and intravenous administration of acetazolamide. After thirty minutes, he recovered perception to light and then hand motion and 2 h later, it was improved to 1 m counting finger. CRAO following orbital tumor has not been reported before. We recommend ocular examination in all patients that undergo orbital surgery immediately to 2–3 h after surgery. 相似文献
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Maria Marx Céline Lebuhotel Danielle Laugier Audrey Chapelle Georges Calothy Simon Saule 《Experimental eye research》2010,90(6):791-801
The aim of this work was to define the role of pRb depletion in the proliferation and differentiation of avian retinoblasts in vitro. For this purpose vectors expressing pRb short hairpin RNA were used to deplete pRb in cultures of avian neuroretinal cells. Down regulation of pRb was observed by Western blot and quantification of nuclear pRb. Cell proliferation and differentiation were studied following BrdU labeling and immunostaining. Transfection significantly down-regulated pRb in neuroretinal cells. Long-term effect of pRb depletion mainly induced proliferation of epithelial-like cells that expressed markers of reactive Müller glial cells. A minority of these cells that survived passaging could be maintained as neurosphere-like aggregates with low pRb, not observed in control cultures. BrdU labeling followed by a two week chase showed the presence of cells still remained labelled, indicating low cell cycling. Under appropriate conditions, these aggregates differentiate in precursors of amacrine interneurons shown by the expression of AP2, in absence of the photoreceptors marker visinin and the late neuronal marker MAP2. Taken together these data show that decrease pRb level in cultures of avian neuroretinal cells promotes the emergence and proliferation of stem cell/progenitors from reactive-like Muller cells. 相似文献
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We present a case of sickle cell-hemoglobin C disease that presented acute retinal and choroidal peripheral non-perfusion
on the base of chronic microvascular obstruction, which transiently closed retinal neovessels. 相似文献
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Cross-talk between microRNA-let7c and transforming growth factor-β2 during epithelial-to-mesenchymal transition of retinal pigment epithelial cells 下载免费PDF全文
AIM: To explore the roles of microRNA-let7c (miR-let7c) and transforming growth factor-β2 (TGF-β2) and cellular signaling during epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells.
METHODS: Retinal pigment epithelial (ARPE-19) cells were cultured with no serum for 12h, and then with recombinant human TGF-β2 for different lengths of time. ARPE-19 cells were transfected with 1×106 TU/mL miR-let7c mimcs (miR-let7cM), miR-let7c mimcs negative control (miR-let7cMNC) and miR-let7c inhibitor (miR-let7cI) using the transfection reagent. The expression of keratin-18, vimentin, N-cadherin, IKB alpha, p65 were detected by Western blot, quantitative polymerase chain reaction and immunofluorescence.
RESULTS: The expression of miR-let7c was dramatically reduced and the nuclear factor-kappa B (NF-κB) signaling pathway was activated after induction by TGF-β2 (P<0.05). In turn, overexpressed miR-let7c significantly inhibited TGF-β2-induced EMT (P<0.05). However, miR-let7c was unable to inhibit TGF-β2-induced EMT when the NF-κB signaling pathway was inhibited by BAY11-7082 (P<0.01).
CONCLUSION: The miR-let7c regulates TGF-β2-induced EMT through the NF-κB signaling pathway in ARPE-19 cells. 相似文献
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Topographic and age-related changes of the retinal epithelium and Bruch’s membrane of rhesus monkeys
Peter Gouras Lena Ivert Martha Neuringer Julie A. Mattison 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2010,248(7):973-984
Purpose
To examine structural differences in the retinal pigmented epithelium (RPE) and Bruch’s membrane of rhesus monkeys (Macaca mulatta) as a function of topography and age. 相似文献12.
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Electrophysiology of rabbit Müller (glial) cells in experimental retinal detachment and PVR 总被引:3,自引:0,他引:3
Francke M Faude F Pannicke T Bringmann A Eckstein P Reichelt W Wiedemann P Reichenbach A 《Investigative ophthalmology & visual science》2001,42(5):1072-1079
PURPOSE: To determine the electrophysiological properties of Müller (glial) cells from experimentally detached rabbit retinas. METHODS: A stable local retinal detachment was induced by subretinal injection of a sodium hyaluronate solution. Müller cells were acutely dissociated and studied by the whole-cell voltage-clamp technique. RESULTS: The cell membranes of Müller cells from normal retinas were dominated by a large inwardly rectifying potassium ion (K+) conductance that caused a low-input resistance (<100 M(Omega)) and a high resting membrane potential (-82 +/- 6 mV). During the first week after detachment, the Müller cells became reactive as shown by glial fibrillary acidic protein (GFAP) immunoreactivity, and their inward currents were markedly reduced, accompanied by an increased input resistance (>200 M(Omega)). After 3 weeks of detachment, the input resistance increased further (>300 M(Omega)), and some cells displayed significantly depolarized membrane potentials (mean -69 +/- 18 mV). When PVR developed (in 20% of the cases) the inward K+ currents were virtually completely eliminated. The input resistance increased dramatically (>1000 MOmega), and almost all cells displayed strongly depolarized membrane potentials (-44 +/- 16 mV). CONCLUSIONS: Reactive Müller cells are characterized by a severe reduction of their K+ inward conductance, accompanied by depolarized membrane potentials. These changes must impair physiological glial functions, such as neurotransmitter recycling and K+ ion clearance. Furthermore, the open probability of certain types of voltage-dependent ion channels (e.g., Ca2+-dependent K+ maxi channels) increases that may be a precondition for Müller cell proliferation, particularly in PVR when a dramatic downregulation of both inward current density and resting membrane potential occurs. 相似文献
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Age-related changes of mitochondria were studied in Müller (retinal glial) cells from guinea pigs fed with or without externally applied Ginkgo biloba extract EGb 761, an established radical scavenger. When Müller cell mitochondria from aged animals were compared with those from young adults, they displayed (1) a diminished number of well-defined cristae at the ultrastructural level, (2) a reduced membrane potential, as revealed by fluorimetry using the voltage-sensitive dye tetramethyl rhodamine methylester, and (3) a slightly reduced index of vitality assayed by tetrazolium salt colorimetry. Müller cell mitochondria were also studied in aged guinea pigs which had been fed daily by EGb 761 during the last 2 months before they were sacrificed. Such mitochondria displayed (1) many well-defined cristae at the ultrastructural level, and, compared with mitochondria from untreated aged animals, (2) a significantly enhanced membrane potential and (3) a significantly enhanced index of vitality. No age- or drug-related changes were observed in the mitochondrial content of GABA transaminase, as revealed by immunocytochemistry/densitometry. These results suggest that many but not all structural and functional parameters of aging Müller cell mitochondria are impaired by accumulating oxidative damage, and that externally applied radical scavengers may protect the organelles from the damaging actions of free radicals. As it has been shown earlier that EGb 761 treatment enhances the intrinsic glutathione content of aged guinea pig Müller cells, the protective radical-scavenging effect of the drug may be mediated both directly and indirectly. 相似文献
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Limiting the proliferation and reactivity of retinal Müller cells during experimental retinal detachment: the value of oxygen supplementation. 总被引:9,自引:0,他引:9
G Lewis K Mervin K Valter J Maslim P J Kappel J Stone S Fisher 《American journal of ophthalmology》1999,128(2):165-172
PURPOSE: To assess the role of hypoxia in inducing the proliferation, hypertrophy, and dysfunction of Muller cells in detached retina and the effectiveness of supplemental oxygen in limiting these reactions. METHODS: Retinal detachments were produced in the right eye of each of 13 cats; the cats survived surgery for 3 days, during which six were kept in normoxia (room air, 21%) and seven in hyperoxia (70% oxygen). Retinas were labeled for proliferation with an antibody (MIB-1) to a cell cycle protein (Ki-67), for evidence of hypertrophy employing antibodies to the intermediate filament protein glial fibrillary acidic protein (GFAP) and to beta-tubulin and for disturbance of glutamate neurochemistry employing antibodies to glutamate to a glutamate receptor (GluR-2) and to glutamine synthetase. RESULTS: Results from the two animals kept in normoxia after retinal detachment confirmed previous reports that detachment caused the proliferation of Muller cells, the hypertrophy of Muller cell processes, and the disruption of glutamate recycling by Muller cells. Oxygen supplementation during detachment reduced Muller cell proliferation and hypertrophy and reduced the abnormalities in the distributions of glutamate, GluR-2, and glutamine synthetase. CONCLUSIONS: Oxygen supplementation reduced the reaction of retinal Muller cells to retinal detachment, limiting their proliferation and helping to maintain their normal structure and function. In the clinical setting, oxygen supplementation between diagnosis and reattachment surgery may reduce the incidence and severity of glial-based complications, such as proliferative vitreoretinopathy. 相似文献
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【In Press】 Application of stem cell-derived retinal pigment epithelium in retinal degenerative diseases: present and future 下载免费PDF全文
Abstract: As a constituent of blood-retinal barrier and retinal outer segment (ROS) scavenger, retinal pigmented epithelium (RPE) is fundamental to normal function of retina. Malfunctioning of RPE contributes to the onset and advance of retinal degenerative diseases. Up to date, RPE replacement therapy is the only possible method to completely reverse retinal degeneration. Transplantation of human RPE stem cell-derived RPE (hRPESC-RPE) has shown some good results in animal models. With promising results in terms of safety and visual improvement, human embryonic stem cell-derived RPE (hESC-RPE) can be expected in clinical settings in the near future. Despite twists and turns, induced pluripotent stem cell-derived RPE (iPSC-RPE) is now being intensely investigated to overcome genetic and epigenetic instability. By far, only one patient has received iPSC-RPE transplant, which is a hallmark of iPSC technology development. During follow-up, no major complications such as immunogenicity or tumorigenesis have been observed. Future trials should keep focusing on the safety of stem cell-derived RPE (SC-RPE) especially in long period, and better understanding of the nature of stem cell and the molecular events in the process to generate SC-RPE is necessary to the prosperity of SC-RPE clinical application. 相似文献
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Patricia Köferl Margrit Hollborn Jiri Rehak Ianors Iandiev Sladjana Dukic-Stefanovic Peter Wiedemann Leon Kohen Andreas Bringmann Matus Rehak 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2014,252(2):257-265
Background
To investigate the effect of induced arteriolar constriction (AC) on alterations in gene expression of factors implicated in the development of edema in branch retinal vein occlusion (BRVO).Methods
In Brown-Norway rats, BRVO was induced by laser photocoagulation of the veins in one half of the retina. AC of the afferent arterioles was performed 30 min later. We then determined the expression of Vegfa, Vegfb, Pedf, Kir4.1, Aqp4, Aqp1, Il1ß, and Il6 with real-time polymerase chain reaction (RT-PCR) in the neuroretina and retinal pigment epithelium (RPE) after 1, 3, and 7 days. Immunostaining against GFAP, aquaporin (AQP)-4, and Kir4.1 was performed on days 1 and 3.Results
BRVO resulted in transient upregulation of Vegfa in the neuroretina on day 1. The expressions of Kir4.1, AQP4, and AQP1 were downregulated, and Il1ß and Il6 were strongly upregulated, on days 1 and 3. The retinal distribution of GFAP and AQP4 proteins remained unaltered, while the Kir4.1 protein displayed redistribution from polarized to uniform retinal distribution. AC accelerated the restoration of downregulated Kir4.1, Aqp4, and Aqp1 in the RPE, of Kir4.1 in the neuroretina, and of upregulated Il6 in the neuroretina. AC did not influence the gliotic alterations of Müller cells and the redistribution of the Kir4.1 protein.Conclusion
Constriction of the afferent artery in the BRVO region accelerated the restoration of potassium channels and Il6. These alterations may contribute to faster resorption of retinal edema, and may decrease the level of inflammation. 相似文献18.
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Background: To explore the potential role of vascular endothelial growth factor compared with transforming growth factor‐β2 in the regulation of human retinal pigment epithelium cell‐mediated collagen gel contraction. Methods: The retinal pigment epithelium cell mediated type I collagen gel contraction assay was performed to evaluate and compare the effect of vascular endothelial growth factor and transforming growth factor‐β2. The number of viable retinal pigment epithelium cells in the gel and the expression of α‐smooth muscle actin were analysed. Results: Both vascular endothelial growth factor and transforming growth factor‐β2 caused a time dependent gel contraction, associated with over expression of α‐smooth muscle actin in retinal pigment epithelium cells undergoing a fibroblast like transformation. The decrease in volume of the collagen gel and increase in α‐smooth muscle actin expression were more significant in the transforming growth factor‐β2‐treated group than in vascular endothelial growth factor‐treated group beginning at day 2, and the growth of retinal pigment epithelium cells was significantly more inhibited in the transforming growth factor‐β2‐treated group compared with the vascular endothelial growth factor‐treated group after day 1 (P < 0.05). Transforming growth factor‐β2 stimulation increased both vascular endothelial growth factor mRNA expression and secretion. The α‐smooth muscle actin expression and the change in volume of collagen gel were significantly positively correlated in both experimental groups. Conclusions: Both vascular endothelial growth factor and transforming growth factor‐β2 can cause induction of retinal pigment epithelium cell‐mediated collagen gel contraction in vitro via partial upregulation of α‐smooth muscle actin expression. 相似文献
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I.-Mo Fang Chang-Hao Yang Chung-May Yang Muh-Shy Chen 《Taiwan Journal of Ophthalmology》2012,2(1):13-17
PurposeTo elucidate the effects of tumor necrosis factor (TNF)-α on the expression of inducible nitric oxide synthase (iNOS) in retinal pigment epithelial cells in vitro.MethodsARPE-19 cell lines were cultured with TNF-α stimulation, and then treated with proteasome inhibitors (MG132 or lactacystin) for 30 minutes. The expression of iNOS was determined by RT-PCR and Western blot. The expression of nitric oxide (NO) was determined by an enzyme-linked immunosorbent assay. The interaction of nuclear factor kappa-B (NF-κB) activation and iNOS induction was assessed by electrophoretic mobility shift assay.ResultsThe expression of iNOS in ARPE-19 was induced by TNF-α in a dose-dependent manner. Upregulation of iNOS resulted in increased production of NO. iNOS induced by TNF-α could be inhibited by MG-132 and lactacystin. Supershift assay revealed that NF-κB activation was responsible for iNOS induction.ConclusionTNF-α could induce iNOS expression and NO production in RPE cells, at least in part, via an NF-κB signal pathway. 相似文献