Database : MEDLINE
Search on : Ocular and Hypertension [Words]
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[PMID]: 29524771
[Au] Autor:Devrukhakar PS; M SS; G S; R S
[Ad] Address:School of Advance Sciences, Vellore Institute of technology (VIT), Katpadi, Vellore, Tamil Nadu 632014, India.
[Ti] Title:Proposal of degradation pathway with toxicity prediction for hydrolytic and photolytic degradation products of timolol.
[So] Source:J Pharm Biomed Anal;154:7-15, 2018 Feb 28.
[Is] ISSN:1873-264X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Timolol (TIM) is a potent ß-adrenergic blocker, useful in treatment of ocular hypertension or open-angle glaucoma. Development and validation of stability indicating LCMS assay method for TIM was accomplished coherent with ICH guideline. Successful chromatographic separation of TIM with its four degradation products was attained by using gradient elution mode on reverse phase column using ammonium acetate buffer, pH 4.6 as mobile phase A and organic solvent as the mobile phase B. Chromatographic conditions were set such as 1.0 mL min flow rate, 20 µL injection volume, 30 °C column temperature and 320 nm detection wavelength. Four major degradation products obtained from hydrolysis and photolysis, were identified and characterized with the combination of liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS/MS) and accurate mass measurements. Degradation pathways were identified based on a comparison of the fragmentation pattern of the [M+H] ions of TIM and its degradation products. The method validation was performed as per ICH guideline Q2 (R1).
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 11967 MEDLINE  
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[PMID]: 29524673
[Au] Autor:Raghunathan V; Benoit J; Kasetti R; Zode G; Salemi M; Phinney BS; Keller KE; Staverosky JA; Murphy CJ; Acott T; Vranka J
[Ad] Address:Department of Basic Sciences, University of Houston, Houston, TX, 77204, USA; The Ocular Surface Institute, University of Houston, Houston, TX, 77204, USA. Electronic address: vraghunathan@uh.edu.
[Ti] Title:Glaucomatous cell derived matrices differentially modulate non-glaucomatous trabecular meshwork cellular behavior.
[So] Source:Acta Biomater;, 2018 Mar 07.
[Is] ISSN:1878-7568
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Ocular hypertension is a causal risk-factor to developing glaucoma. This is associated with stiffening of the trabecular meshwork (TM), the primary site of resistance to aqueous-humor-outflow. The mechanisms underlying this stiffening or how pathologic extracellular matrix (ECM) affects cell function are poorly understood. It is recognized that mechanotransduction systems allow cells to sense and translate the intrinsic biophysical properties of ECM into intracellular signals to control gene transcription, protein expression, and cell behavior. Using an anterior segment perfusion model, we document that there are significantly more low flow regions that are much stiffer, and fewer high flow regions that are less stiff in glaucomatous TM (GTM) when compared to non-glaucomatous TMs (NTM). GTM tissue also has fewer cells overall when compared with NTM tissue. In order to study the role of pathologic ECM in glaucoma disease progression, we conducted studies using cell derived matrices (CDM). First, we characterized the mechanics, composition and organization of fibronectin in ECM deposited by GTM and NTM cells treated with glucocorticosteroids. Then, we determined that these GTM-derived ECM are able to induce stiffening of normal NTM cells, and alter their gene/protein expression to resemble that of a glaucomatous phenotype. Further, we demonstrate that GTM-derived ECM causes endoplasmic reticular stress in NTM. They also became resistant to being reorganized by these NTM cells. These phenomena were exacerbated by ECMs obtained from steroid treated glaucoma model groups. Collectively, our data demonstrates that CDMs represent a novel tool for the study of bidirectional interactions between TM cells and their immediate microenvironment. STATEMENT OF SIGNIFICANCE: Extracellular matrix (ECM) changes are prevalent in a number of diseases. The precise mechanisms by which changes in the ECM contribute to disease progression is unclear, primarily due to absence of appropriate models. Here, using glaucoma as a disease model, we document changes in cell derived matrix (CDM) and tissue mechanics that contribute to the pathology. Subsequently, we determine the effect that ECMs from diseased and healthy individuals have on healthy cell behaviors. Data emanating from this study demonstrate that CDMs are a potent tool for the study of cell-ECM interactions.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  3 / 11967 MEDLINE  
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[PMID]: 29523993
[Au] Autor:Edlinger FSM; Schrems-Hoesl LM; Mardin CY; Laemmer R; Kruse FE; Schrems WA
[Ad] Address:Department of Ophthalmology, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.
[Ti] Title:Structural changes of macular inner retinal layers in early normal-tension and high-tension glaucoma by spectral-domain optical coherence tomography.
[So] Source:Graefes Arch Clin Exp Ophthalmol;, 2018 Mar 09.
[Is] ISSN:1435-702X
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:PURPOSE: Assessment of the diagnostic ability of segmented macular inner retinal layer thickness and peripapillary retinal nerve fiber layer (pRNFL) measured by spectral-domain optical coherence tomography (SD-OCT) in patients with normal-tension (NT) and high-tension (HT) perimetric and preperimetric glaucoma. METHODS: The 212 participants included 45 healthy subjects, 55 patients with ocular hypertension, 56 patients with preperimetric glaucoma, and 56 patients with perimetric glaucoma. The preperimetric and perimetric groups were further subdivided into NT and HT groups. Sectoral and global thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (mGCL), inner plexiform layer (mIPL), ganglion cell complex (mGCC), and pRNFL were measured using SD-OCT (Spectralis, Heidelberg Engineering, Germany). Diagnostic performance was ascertained by sectoral and global comparison of the sensitivities at specificity ≥ 95%. RESULTS: For all layers, the largest thickness decrease was reported in the HT perimetric group. In all groups, the sensitivities of mGCL showed a comparable diagnostic value to pRNFL in order to distinguish between healthy subjects and glaucoma patients. In the perimetric group, mGCL (85.7%) exhibited higher sensitivities than mRNFL (78.6%) and mGCC (78.6%). Both mRNFL and pRNFL demonstrated equal diagnostic performance in the HT perimetric group (88.5 and 96.2%), in the NT groups, mRNFL was inferior to all other layers. CONCLUSION: The sensitivities of mGCL and mRNFL were comparable to the sensitivities of pRNFL. In clinical application, mGCL and mRNFL, with a focus on the temporal and inferior sectors, may provide a convincing supplementation to pRNFL. CLINICAL TRIAL REGISTRATION: Erlangen Glaucoma Registry www.clinicaltrials.gov ID: NCT00494923.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[Cl] Clinical Trial:ClinicalTrial
[St] Status:Publisher
[do] DOI:10.1007/s00417-018-3944-6

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[PMID]: 29520478
[Au] Autor:Chihara E; Dimitrova G; Chihara T
[Ad] Address:Sensho-kai Eye Institute, Minamiyama 50-1, Iseda, Uji, Kyoto, 611-0043, Japan. chihara-oph@umin.net.
[Ti] Title:Increase in the OCT angiographic peripapillary vessel density by ROCK inhibitor ripasudil instillation: a comparison with brimonidine.
[So] Source:Graefes Arch Clin Exp Ophthalmol;, 2018 Mar 08.
[Is] ISSN:1435-702X
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:PURPOSE: To assess the responses of the superficial peripapillary retinal vessel density (VD) and prelaminar flow index (PLFI) to topical Rho-assisted coiled-coil forming protein kinase (ROCK) inhibitor ripasudil and alpha-2 agonist brimonidine using optical coherence tomography angiography. METHODS: This is a prospective, non-randomized, comparative cohort study. We studied the response of optical coherence tomography angiography (OCTA) parameters to drugs in 24 eyes treated with ripasudil and 23 eyes treated with brimonidine at the Sensho-kai Eye Institute. After division by the signal strength (SS), we compared the responses of peripapillary VD/SS and PLFI/unit area (UA)/SS to topical eye drops in eyes with primary open-angle glaucoma (POAG) and ocular hypertension (OH). RESULTS: In the superficial peripapillary retina, VD/SS increased significantly in the ripasudil-treated eyes (12.5 ± 21.7%, P = 0.018), but not in the brimonidine-treated eyes (- 2.0 ± 13.8%, P = 0.484). In the deeper area of the optic disc, the changes in the PLFI/UA/SS in the brimonidine-treated eyes (+ 0.9 ± 8.9%, P = 1.00) and ripasudil-treated eyes (- 1.3 ± 8.5%, P = 0.241) were not significant. Multivariate discriminant analysis showed that the change in the peripapillary VD/SS was the most important parameter (P = 0.0186) for differentiating ripasudil- and brimonidine-treated eyes. CONCLUSIONS: The topical ROCK inhibitor ripasudil enhanced the peripapillary VD in POAG and OH, whereas the alpha-2 agonist brimonidine did not. The PLFI did not respond to either drug.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1007/s00417-018-3945-5

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[PMID]: 29309745
[Au] Autor:Tsai SH; Xie W; Zhao M; Rosa RH; Hein TW; Kuo L
[Ad] Address:Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple; and the Ophthalmic Vascular Research Program, Department of Ophthalmology, Scott & White Eye Institute, Baylor Scott & White Health, Temple, Texas.
[Ti] Title:Alterations of Ocular Hemodynamics Impair Ophthalmic Vascular and Neuroretinal Function.
[So] Source:Am J Pathol;188(3):818-827, 2018 Mar.
[Is] ISSN:1525-2191
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Hypertension is associated with numerous diseases, but its direct impact on the ocular circulation and neuroretinal function remains unclear. Herein, mouse eyes were challenged with different levels of hemodynamic insult via transverse aortic coarctation, which increased blood pressure and flow velocity by 50% and 40%, respectively, in the right common carotid artery, and reduced those parameters by 30% and 40%, respectively, in the left common carotid artery. Blood velocity in the right central retinal artery gradually increased up to 40% at 4 weeks of transverse aortic coarctation, and the velocity in the left central retinal artery gradually decreased by 20%. The fundus and retinal architecture were unaltered by hemodynamic changes. Endothelium-dependent vasodilations to acetylcholine and adenosine were reduced only in right (hypertensive) ophthalmic arteries. Increased cellularity in the nerve fiber/ganglion cell layers, enhanced glial fibrillary acidic protein expression, and elevated superoxide level were found only in hypertensive retinas. The electroretinogram showed decreased scotopic b-waves in the hypertensive eyes and decreased scotopic oscillatory potentials in both hypertensive and hypotensive eyes. In conclusion, hypertension sustained for 4 weeks causes ophthalmic vascular dysfunction, retinal glial cell activation, oxidative stress, and neuroretinal impairment. Although ophthalmic vasoregulation is insensitive to hypotensive insult, the ocular hypoperfusion causes neuroretinal dysfunction.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review

  6 / 11967 MEDLINE  
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[PMID]: 29425312
[Au] Autor:Annam K; Chen AJ; Lee IM; Paul AA; Rivera JJ; Greenberg PB
[Ad] Address:Section of Ophthalmology, VA Medical Center, 830 Chalkstone Ave, Providence, RI 02908.
[Ti] Title:Risk Factors for Early Intraocular Pressure Elevation After Cataract Surgery in a Cohort of United States Veterans.
[So] Source:Mil Med;, 2018 Feb 07.
[Is] ISSN:1930-613X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Introduction: Cataract surgery is the most frequently performed surgery in the Veterans Health Administration (VHA). A well-known complication is a transient but potentially harmful elevation in intraocular pressure (IOP) within the 24-h postoperative period. The purpose of this study is to investigate the risk factors for IOP elevation 1 d after cataract surgery in a cohort of United States (US) veterans. Materials and Methods: The study included 784 patients who underwent cataract surgery between April 2013 and April 2016 at a single Veterans Affairs medical center in Providence, RI. One thousand one hundred thirty-seven cataract surgeries were considered in total. Institutional Review Board (IRB) approval was obtained through the Providence Veterans Affairs Medical Center (PVAMC). Logistic regression, adjusted for patients with bilateral surgeries, was used to evaluate risk factors for first postoperative day IOP elevation (≥28 mmHg). The main outcome measure was elevated IOP on postoperative day 1 (POD1) after cataract surgery. Results: The average patient age was 74 yr. Ninety-eight percent (1,110/1,137) of cases involved male patients; 75.3% (856/1,137) of the cataract surgeries were performed by resident surgeons. Type II diabetes mellitus (DM) was present in 41% (461/1,137), alpha-1 blocker use in 31% (358/1,137), ocular hypertension (ocular HTN) in 4% (44/1,137), and glaucoma in 11% (126/1,137) of cases. Twenty-two percent (232/1,137) of eyes had elevated IOP. Independent risk factors were a history of ocular HTN (OR: 8.74 [4.03-18.9]), glaucoma (OR: 3.54 [2.17-5.75]), a preoperative IOP ≥22 mmHg (OR: 2.51 [1.12-5.62]), and complicated cataract surgery (OR: 2.45 [1.18-5.08]), defined as vitreous loss, anterior capsular tear (ACT), posterior capsular tear (PCT), or presence of zonular lysis. Conclusion: These findings suggest that cataract surgery patients with ocular HTN, glaucoma, a preoperative IOP ≥22 mmHg, or significant intraocular complications may benefit from prophylactic ocular anti-hypertensive medication.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1093/milmed/usx113

  7 / 11967 MEDLINE  
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[PMID]: 29510226
[Au] Autor:Wong ABC; Wang MTM; Liu K; Prime ZJ; Danesh-Meyer HV; Craig JP
[Ad] Address:Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, New Zealand.
[Ti] Title:Exploring topical anti-glaucoma medication effects on the ocular surface in the context of the current understanding of dry eye.
[So] Source:Ocul Surf;, 2018 Mar 03.
[Is] ISSN:1937-5913
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: To assess tear film parameters, ocular surface characteristics, and dry eye symptomology in patients receiving topical anti-glaucoma medications. METHODS: Thirty-three patients with a diagnosis of open angle glaucoma or ocular hypertension, receiving unilateral topical anti-glaucoma medication for at least 6 months, were recruited in a cross-sectional, investigator-masked, paired-eye comparison study. Tear film parameters, ocular surface characteristics, and dry eye symptomology of treated and fellow eyes were evaluated and compared. RESULTS: The mean ±â€¯SD age of the participants was 67 ±â€¯12 years, and the mean ±â€¯SD treatment duration was 5.3 ±â€¯4.4 years. Treated eyes had poorer non-invasive tear film break-up time (p = 0.03), tear film osmolarity (p = 0.04), bulbar conjunctival hyperaemia (p = 0.04), eyelid margin abnormality grade (p = 0.01), tear meniscus height (p = 0.03), and anaesthetised Schirmer value (p = 0.04) than fellow eyes. There were no significant differences in dry eye symptomology, meibomian gland assessments, and ocular surface staining between treated and fellow eyes (all p > 0.05). CONCLUSIONS: Adverse changes in tear film stability, tear osmolarity, conjunctival hyperaemia, and eyelid margins were observed in treated eyes. This suggests that inflammatory mechanisms may be implicated in the development of dry eye in patients receiving long term topical anti-glaucoma therapy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:Publisher

  8 / 11967 MEDLINE  
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[PMID]: 29508439
[Au] Autor:Wu HJ; Li XY; Qian WJ; Li Q; Wang SY; Ji M; Ma YY; Gao F; Sun XH; Wang X; Miao Y; Yang XL; Wang Z
[Ad] Address:Department of Neurology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
[Ti] Title:Dopamine D1 receptor-mediated upregulation of BK currents modifies Müller cell gliosis in a rat chronic ocular hypertension model.
[So] Source:Glia;, 2018 Mar 06.
[Is] ISSN:1098-1136
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Müller cell gliosis is a common response in many retinal pathological conditions. We previously demonstrated that downregulation of Kir channels contributes to Müller cell gliosis in a rat chronic ocular hypertension (COH) model. Here, the possible involvement of outward K currents in Müller cell gliosis was investigated. Outward K current densities in Müller cells isolated from COH rats, as compared with those in normal rats, showed a significant increase, which was mainly contributed by large-conductance Ca -activated K (BK ) channels. The involvement of BK channels in Müller cell gliosis is suggested by the fact that glial fibrillary acidic protein (GFAP) levels were augmented in COH retinas when these channels were suppressed by intravitreal injections of iberiotoxin. In COH retinas an increase in dopamine (DA) D1 receptor (D1R) expression in Müller cells was revealed by both immunohistochemistry and Western blotting. Moreover, protein levels of tyrosine hydroxylase were also increased, and consistent to this, retinal DA contents were elevated. SKF81297, a selective D1R agonist, enhanced BK currents of normal Müller cells through intracellular cAMP-PKA signaling pathway. Furthermore, GFAP levels were increased by the D1R antagonist SCH23390 injected intravitreally through eliminating the BK current upregulation in COH retinas, but partially reduced by SKF81297. All these results strongly suggest that the DA-D1R system may be activated to a stronger extent in COH rat retinas, thus increasing BK currents of Müller cells. The upregulation of BK channels may antagonize the Kir channel inhibition-induced depolarization of Müller cells, thereby attenuating the gliosis of these cells.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:Publisher
[do] DOI:10.1002/glia.23321

  9 / 11967 MEDLINE  
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[PMID]: 29508190
[Au] Autor:Sihota R; Selvan H; Sharma A; Gupta A; Gupta V; Dada T; Upadhyay AD
[Ad] Address:Glaucoma Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, 110029, India.
[Ti] Title:Long-term evaluation of ocular hypertension with primary angle closure and primary open angles.
[So] Source:Int Ophthalmol;, 2018 Mar 05.
[Is] ISSN:1573-2630
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:PURPOSE: To evaluate the long-term course of primary angle-closure ocular hypertension and primary open-angle ocular hypertension and possible risk factors for progression to glaucoma. METHODS: A total of 109 eyes of 109 ocular hypertension (OHT) patients with a minimum follow-up period of 5 years having complete ocular/medical records were evaluated. They were classified into primary angle closure or primary open angle based on gonioscopy at baseline. Baseline and review data of Humphrey field analyser, HFA, and Heidelberg retinal tomography, HRT, were recorded. Guided progression analysis (GPA) and univariate Cox regression were used for time to event analysis in identifying progression to glaucoma. RESULTS: Over a mean follow-up of 12.18 ± 4.8 years, progression to glaucoma was 17.43% (19 eyes), out of whom 5.5% (6 eyes) showed ≥ 3 loci on GPA. Sub-classifying them, progression to primary angle-closure glaucoma was 19.72%, and that of primary open-angle glaucoma was 13.16%. The mean time to progression was 9.34 ± 3.6 years. Significant risk factors included small disc area (≤ 1.99 sq.mm on HRT), requirement of ≥ 2 drugs to maintain target IOP and those engaged in activities yielding a Valsalva effect in daily life. Coronary artery disease (CAD) and systemic use of steroids were associated with increased severity. CONCLUSION: Overall progression of OHT to glaucoma was 17.43% over a mean of 9 years, with target IOP of ≤ 18 mm Hg. Patients with smaller discs, CAD, exercising Valsalva type activities and using ≥ 2 glaucoma medications or systemic steroids should be closely monitored.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:Publisher
[do] DOI:10.1007/s10792-018-0872-8

  10 / 11967 MEDLINE  
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[PMID]: 29505314
[Au] Autor:Ji S; Lin S; Chen J; Huang X; Wei CC; Li Z; Tang S
[Ad] Address:a Aier School of Ophthalmology , Central South University , Changsha , Hunan , China.
[Ti] Title:Neuroprotection of Transplanting Human Umbilical Cord Mesenchymal Stem Cells in a Microbead Induced Ocular Hypertension Rat Model.
[So] Source:Curr Eye Res;:1-11, 2018 Mar 05.
[Is] ISSN:1460-2202
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:PURPOSE: The purpose of this study is to investigate the potential therapeutic benefits of intravitreally transplanted human umbilical cord mesenchymal stem cells (UC-MSCs) in an animal model of microbead-injection-induced ocular hypertension (OHT). METHODS: UC-MSCs were isolated from human umbilical cords and then cultured. The OHT model was induced via intracameral injection of polystyrene microbeads in Sprague-Dawley adult rat eyes. Fifty-four healthy adult rats were randomly divided into three groups: normal control, OHT model treated with intravitreal transplantation of UC-MSCs, or phosphate-buffered saline (PBS). Two days after OHT was induced, either 5 µl 10 UC-MSCs suspension or PBS was injected into the vitreous cavity of rats. UC-MSCs localization and integration were examined via immunohistochemistry. Neuroprotection was quantified by counting retinal ganglion cells (RGCs) and axons 2 weeks following transplantation. The expression levels of glial-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) were assessed via immunohistochemistry and Western blot. Functional recovery was assessed 2 weeks after transplantation via scotopic threshold response (STR) electroretinography. RESULTS: Elevated IOP levels were sustained at least 3 weeks after intracameral microbead injection and the number of ß-III-tubulin RGCs significantly declined compared to PBS-injected eyes. UC-MSCs survived for at least 2 weeks after intravitreal transplantation and predominantly located in the vitreous cavity. A fraction of cells migrated into the ganglion cell layer of host retina, but without differentiation. Intravitreal UC-MSC transplantation resulted in increased number of RGCs, axons, and increased expression of GDNF and BDNF but decreased expression of GFAP. Intravitreal delivery of UC-MSCs significantly improved the recovery of the positive STR. CONCLUSIONS: Intravitreal transplantation of UC-MSCs revealed the neuroprotection in the microbead-injection induced OHT. The effects could be related to the secretion of tropic factors (BDNF and GDNF) and the modulation of glial cell activation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:Publisher
[do] DOI:10.1080/02713683.2018.1440604


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