Dataset Information

Timolol maleate, a β blocker eye drop, improved edema in a retinal vein occlusion model.

ABSTRACT:

Purpose

To investigate the therapeutic effects of eye drops, namely, timolol maleate, a β-adrenergic receptor antagonist, and latanoprost, a prostaglandin F2α analog, on retinal edema in a murine retinal vein occlusion (RVO) model.

Methods

An RVO model was established using laser-induced RVO in mice, which were administered timolol maleate and latanoprost eye drops several times after venous occlusion. Subsequently, the thickness of the inner nuclear layer (INL) and the expression levels of such genes as Vegf and Atf4, which are stress markers of the endoplasmic reticulum, were examined. Primary human cultured retinal microvascular endothelial cells (HRMECs) were treated with timolol under hypoxic conditions, after which the gene expression pattern was investigated. Importantly, an integrated stress response inhibitor (ISRIB) was used in the RVO model, he known ISRIB, which suppresses the expression of ATF4 in retinal edema.

Results

Increased INL thickness was suppressed by timolol eye drops, as were the expressions of Vegf and Atf4, in the RVO model. However, latanoprost eye drops did not induce any change in INL thickness. In HRMECs, hypoxic stress and serum deprivation increased the Vegf and Atf4 expressions; in response, treatment with timolol suppressed the Vegf expression. Furthermore, the ISRIB decreased the Vegf expression pattern and edema formation, which are associated with RVO.

Conclusions

These results indicate that timolol eye drops may be a potential option for RVO treatment.

SUBMITTER: Fuma S

PROVIDER: S-EPMC10784217 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Timolol maleate, a β blocker eye drop, improved edema in a retinal vein occlusion model.

Fuma Shinichiro S Hidaka Yae Y Nishinaka Anri A Yasuda Hiroto H Aoshima Kota K Nakamura Shinsuke S Hara Hideaki H Shimazawa Masamitsu M

Molecular vision 20231015

<h4>Purpose</h4>To investigate the therapeutic effects of eye drops, namely, timolol maleate, a β-adrenergic receptor antagonist, and latanoprost, a prostaglandin F2α analog, on retinal edema in a murine retinal vein occlusion (RVO) model.<h4>Methods</h4>An RVO model was established using laser-induced RVO in mice, which were administered timolol maleate and latanoprost eye drops several times after venous occlusion. Subsequently, the thickness of the inner nuclear layer (INL) and the expression ...[more]

PMID: 38222457

Similar Datasets

Project description:PurposeTo assess the relationship between best-corrected visual acuity (BCVA) and anatomic features in patients with macular edema (ME) related to retinal vein occlusion (RVO).DesignPost hoc analysis of 3 clinical trials, which included verified diagnoses, protocol refractions, and the assessment of OCT and fluorescein angiography (FA) images at a masked reading center.ParticipantsPatients diagnosed with RVO-ME.MethodsCorrelation analyses were performed to determine the correlation between BCVA and macular anatomy at baseline and at 12 and 24 weeks and between changes from baseline to 12 and 24 weeks.Main outcome measuresThe correlations between BCVA and central subfield thickness (CST), ellipsoid zone (EZ) integrity, intraretinal fluid (IRF), subretinal fluid, central leakage, and ischemia were assessed.ResultsIn a total of 828 eyes with RVO-ME, the mean age, BCVA, and CST at baseline was 64.7 years, 51.1 letters, and 656.9 μm, respectively. At baseline, a moderate negative correlation was observed between BCVA and CST (r = - 0.56, P < 0.001). At weeks 12 and 24, the mean BCVA of eyes with definitely abnormal (absent) EZ was statistically significantly worse than that of eyes with normal EZ. At week 12, a moderate negative correlation was observed between changes in BCVA and changes in CST (r = - 0.35, P < 0.001), with a similar degree of association noted at week 24 (r = - 0.35, P < 0.001). At weeks 12 and 24, eyes that showed any improvement in central IRF showed a greater improvement in BCVA than eyes that showed no improvement worsening (week 12: 463 eyes, 18.3 letters vs. 177 eyes, 13.0 letters, respectively, P < 0.001) and (week 24: 332 eyes, 20.2 letters vs. 131 eyes, 13.3 letters, respectively, P < 0.001). With respect to the correlation between baseline BCVA and fluorescein leakage or capillary nonperfusion, the Pearson correlation coefficients were - 0.41 (P < 0.001) and - 0.16 (P = 0.060), respectively.ConclusionsIn addition to CST, there are important clinically relevant relationships between BCVA and both OCT and FA anatomic features in patients with RVO-ME.

Project description:BackgroundThe comparative safety and efficacy of different doses of intravitreal triamcinolone acetonide (IVTA) for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is unclear.ObjectivesThis meta-analysis aimed to compare the safety and efficacy of different doses of IVTA in this setting.MethodsA systematic literature search for randomized clinical trials (RCTs) was conducted on Cochrane Library, Ovid MEDLINE, and EMBASE from January 2005 to May 2022. Studies that reported on patients with DME or ME secondary to RVO that received treatment with different doses of IVTA were included. A random-effects meta-analysis was performed. Cochrane's Risk of Bias Tool 2 was used to assess the risk of bias, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were used to assess certainty of evidence.ResultsFive RCTs reporting on 1,041 eyes at baseline were included in this meta-analysis. In eyes with ME secondary to RVO, high-dose (4 mg) IVTA achieved a significantly better change in best-corrected visual acuity (WMD = -4.75 ETDRS letters, 95% CI = [-7.73, -1.78], p = 0.002) and reduction in retinal thickness (WMD = -93.02 μm, 95% CI = [-153.23, -32.82], p = 0.002) at months 4-6 compared to low-dose (1-2 mg) IVTA. However, high-dose IVTA had a higher risk of intraocular pressure-related adverse events (RR = 2.99, 95% CI = [1.05, 8.50], p = 0.04) and cataract surgery (RR = 5.67, 95% CI = [3.09, 10.41], p < 0.00001) than low-dose IVTA in eyes with ME secondary to RVO. These efficacy and safety differences in high-dose and low-dose IVTA were not observed in DME eyes.ConclusionsThe RCT evidence in this setting is limited. High-dose IVTA achieved greater improvements in visual acuity and reductions in retinal thickness than low-dose IVTA at months 4-6. However, high-dose IVTA had a less favorable safety profile than low-dose IVTA. The significance of these outcomes was based on patients with ME secondary to RVO, but not DME.

Project description:BackgroundCentral retinal vein occlusion (CRVO) is a common retinal vascular disorder in which macular edema (ME) may develop, with a consequent reduction in visual acuity. The visual prognosis in CRVO-ME is poor in a substantial proportion of patients, especially those with the ischemic subtype, and until recently there has been no treatment of proven benefit. Macular grid laser treatment is ineffective, and whilst a few recent randomized controlled trials (RCTs) suggest short-term gains in visual acuity with intravitreal steroids for patients with non-ischemic CRVO-ME, there is no established treatment for ischemic CRVO-ME. Anti-vascular endothelial growth factor (anti-VEGF) agents have been used to treat ME resulting from a variety of causes and may represent a treatment option for CRVO-ME.ObjectivesTo investigate the effectiveness and safety of intravitreal anti-VEGF agents in the treatment of CRVO-ME.Search strategyWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 8), MEDLINE (January 1950 to August 2010), EMBASE (January 1980 to August 2010), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2010), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to August 2010), OpenSIGLE (January 1950 to August 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 10 August 2010.Selection criteriaWe considered RCTs that compared intravitreal anti-VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender with unilateral or bilateral disease and a minimum of six months follow up. Secondarily, we considered non-randomized studies with the same criteria, but did not conduct a separate electronic search for these.Data collection and analysisTwo review authors independently assessed trial quality and extracted data.Main resultsWe found two RCTs that met the inclusion criteria after independent and duplicate review of the search results. These RCTs utilized different anti-VEGF agents which cannot be assumed to be directly comparable. We, therefore, performed no meta-analysis. Evidence from these trials and from other non-randomized case series is summarized in this review.Authors' conclusionsRanibizumab and pegaptanib sodium have shown promise in the short-term treatment of non-ischemic CRVO-ME. However, effectiveness and safety data from larger RCTs with follow up beyond six months are not yet available. There are no RCT data on anti-VEGF agents in ischemic CRVO-ME. The use of anti-VEGF agents to treat this condition therefore remains experimental.

Dataset Information

Timolol maleate, a β blocker eye drop, improved edema in a retinal vein occlusion model.

Purpose

Methods

Results

Conclusions

Publications

Timolol maleate, a β blocker eye drop, improved edema in a retinal vein occlusion model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets