scholarly journals Astragaloside IV Attenuates Ocular Hypertension in a Mouse Model of TGFβ2 Induced Primary Open Angle Glaucoma

2021 ◽  
Vol 22 (22) ◽  
pp. 12508
Author(s):  
Ramesh B. Kasetti ◽  
Prabhavathi Maddineni ◽  
Bindu Kodati ◽  
Bhavani Nagarajan ◽  
Sam Yacoub
Keyword(s):  
Er Stress ◽  
Ocular Hypertension ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Matrix Metalloproteases ◽  
Eye Drops ◽  
Open Angle ◽  
Astragaloside Iv

Elevated intraocular pressure (IOP) is a major risk factor in developing primary open angle glaucoma (POAG), which is the most common form of glaucoma. Transforming growth factor-beta 2 (TGFβ2) is a pro-fibrotic cytokine that plays an important role in POAG pathogenesis. TGFβ2 induced extracellular matrix (ECM) production, deposition and endoplasmic reticulum (ER) stress in the trabecular meshwork (TM) contribute to increased aqueous humor (AH) outflow resistance and IOP elevation. Drugs which alter the glaucomatous fibrotic changes and ER stress in the TM may be effective in reducing ocular hypertension. Astragaloside IV (AS.IV), a novel saponin isolated from the roots of Astragalus membranaceus, has demonstrated antifibrotic and ER stress lowering effects in various tissues during disease conditions. However, the effect of AS.IV on glaucomatous TM fibrosis, ER stress and ocular hypertension has not been studied. Primary human TM cells treated with AS.IV decreased TGFβ2 induced ECM (FN, Col-I) deposition and ER stress (KDEL, ATF4 and CHOP). Moreover, AS.IV treatment reduced TGFβ2 induced NF-κB activation and αSMA expression in TM cells. We found that AS.IV treatment significantly increased levels of matrix metalloproteases (MMP9 and MMP2) and MMP2 enzymatic activity, indicating that the antifibrotic effects of AS.IV are mediated via inhibition of NF-κB and activation of MMPs. AS.IV treatment also reduced ER stress in TM3 cells stably expressing mutant myocilin. Interestingly, the topical ocular AS.IV eye drops (1 mM) significantly decreased TGFβ2 induced ocular hypertension in mice, and this was associated with a decrease in FN, Col-1 (ECM), KDEL (ER stress) and αSMA in mouse TM tissues. Taken together, the results suggest that AS.IV prevents TGFβ2 induced ocular hypertension by modulating ECM deposition and ER stress in the TM.

Topical Bimatoprost Insert for Primary Open-Angle Glaucoma and Ocular Hypertension Treatment - A Phase II Controlled Study

2021 ◽  
Vol 18 ◽  
Author(s):  
Francine Rubião ◽  
Alan Cezar Faria Araújo ◽  
João Bernardo Sancio ◽  
Bárbara Silva Nogueira ◽  
Juçara Ribeiro Franca ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
T Test ◽  
Controlled Study ◽  
Therapeutic Drug ◽  
Eye Drops ◽  
Open Angle ◽  
Drug Concentrations

Background: The most common treatment for primary open-angle glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and ocular hypertension (OH). Methods: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and ≤30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP≤14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, we used a two-way analysis of variance (ANOVA), Student t-test, and paired t-test. Results: Sixteen POAG and 13 OH patients with a mean age of 61 years were assessed. In both eyes, IOP reduction was similar during three weeks of follow-up (19.5±2.2 mmHg and 16.9±3.1 mmHg), insert, and eye drop, respectively; P=0.165). The percentage of IOP reduction in the third week was 30% for insert and 35% for eye drops (P=0.165). No intolerance or discomfort with the insert was reported. Among the research participants, 58% preferred the use of the insert while 25% preferred eye drops, and 17% reported no preference. Conclusions: Bimatoprost-loaded inserts showed similar efficacy to daily bimatoprost eye drops during three weeks of follow up, without major side effects. This might suggest a possible change in the daily therapeutic regimen for the treatment of POAG and OH.

scholarly journals Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2421
Author(s):  
Saray Tabak ◽  
Sofia Schreiber-Avissar ◽  
Elie Beit-Yannai
Keyword(s):  
Oxidative Stress ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Additional Treatment ◽  
Type I ◽  
Open Angle ◽  
Outflow Resistance ◽  
Stress Injury

Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.

scholarly journals A Comparative Analysis of the Efficacy and Safety of fixed Combinations of Latanoprost/Timolol vs Dorzolamide/Timolol in Primary Open Angle Glaucoma or Ocular Hypertension

2012 ◽  
Vol 46 (4) ◽  
pp. 172-176
Author(s):  
Sukhsagar Ratol ◽  
Rani Walia ◽  
Mridu Chaudhry
Keyword(s):  
Ocular Hypertension ◽  
Primary Open Angle Glaucoma ◽  
Fixed Combination ◽  
Open Angle Glaucoma ◽  
Eye Drops ◽  
Open Angle ◽  
Once Daily ◽  
Group 2 ◽  
Diurnal Iop ◽  
Group 1

ABSTRACT Background Glaucoma is a leading cause of irreversible blindness. The fundamental problem in medical management of glaucoma is of patient compliance. An ideal drug or a drug combination is needed to slow the progression of this majorly symptomless disease. Aim To compare the efficacy and tolerability of the fixed combination latanoprost and timolol instilled once daily in the evening vs fixed combination of dorzolamide and timolol instilled twice daily in primary open angle glaucoma or ocular hypertension. Materials and methods A 12-week, randomized, open, parallel group study including 50 patients with primary open angle glaucoma or ocular hypertension was conducted at a tertiary care hospital. Patients were randomized to group 1, (fixed combination (FC) latanoprost and timolol eye drops, once daily in evening) and group 2, (FC dorzolamide and timolol eye drops, twice daily). At baseline, 2, 4 and 12 weeks, IOP was recorded at 9 AM and 12 noon. The difference in IOP reduction in two treatment groups from baseline to 12 weeks was the main outcome measure. Results Mean diurnal IOP was similar at baseline for both groups. Mean reduction in IOP from baseline to 12 weeks was 9.92 mm Hg (p = 0.001) in group 1 and 9.22 (p = 0.001) in group 2. The reduction in IOP in both groups 1 and 2 was statistically significant at all time intervals. There was a statistically significant advantage for group 1 at 12 weeks for both time readings (p = 0.013 and 0.002 respectively) as compared to group 2. Conclusion The fixed combination of latanoprost and timolol was more effective than that of dorzolamide and timolol in reducing mean diurnal IOP and both treatments were well tolerated. To confirm further such studies are required. How to cite this article Ratol S, Walia R, Chaudhry M. A Comparative Analysis of the Efficacy and Safety of fixed Combinations of Latanoprost/Timolol vs Dorzolamide/Timolol in Primary Open Angle Glaucoma or Ocular Hypertension. J Postgrad Med Edu Res 2012;46(4):172-176.

scholarly journals THE EFFECTIVITY OF LEVOBUNOLOL VERSUS TRAVOPROST IN REDUCING INTRAOCULAR PRESSURE

2021 ◽  
Vol 29 (02) ◽  
pp. 93-97
Author(s):  
Falak Naz ◽  
Muhammad Saleh Faisal ◽  
Waheed Iqbal ◽  
Momina Naz ◽  
Muhammad sajid Khan ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Demographic Data ◽  
P Value ◽  
Eye Drops ◽  
Open Angle ◽  
Efficacy Evaluation ◽  
Onset Of Action

ABSTRACT Objective: To compare levobunolol and travoprost for lowering the intra-ocular pressure (IOP) in patients of ocular hypertension and primary open-angle glaucoma. Materials and Methods: A Quasi experimental study was conducted in the ophthalmology department of Khyber Teaching Hospital, Peshawar. 120 patients of both genders and age between 18-80 years with ocular hypertension or primary open angle glaucoma requiring single pressure lowering drug were enrolled in the study. Subjects were divided into two groups (60 in each). One group was treated with travoprost eye drops (0.004%, OD) while other group with levobunolol eye drops (0.5%, OD). After initial screening visit where demographic data and baseline IOP was recorded on structured proforma, three follow-up visits were arranged each at 02 weeks interval. At each follow-up visit, IOP was recorded by standard protocols to evaluate and compare the ocular hypotensive efficacy of study drugs by calculating mean IOP change from the baseline. Only patients with no missing IOP measurements for all visits were considered eligible for the efficacy evaluation. Results: A total of 120 patients were observed having age range from 18 years and above with mean age 52.16 ± 9.56 and predominance of male gender. Upon comparative analysis, no significant statistical difference (p value >0.05) was observed in the ocular hypotensive efficacy of levobunolol and travoprost measured at each follow-up visit, indicating both the drugs equally effective. Moreover, age groups did not reveal any significant statistical impact on the treatment outcome of patients treated with either study drug. Conclusion: Though both the drugs are equally effective, levobunolol is better option than travoprost for the treatment of glaucoma because of its fast onset of action, cost effectiveness and easy availability.

Genetic analysis of primary open-angle glaucoma-related risk alleles in a Korean population: the GLAU-GENDISK study

2020 ◽  
pp. bjophthalmol-2020-316089
Author(s):  
Yong Woo Kim ◽  
Yun Hwan Lee ◽  
Jin-Soo Kim ◽  
Jinho Lee ◽  
Yu Jeong Kim ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Coiled Coil ◽  
Korean Population ◽  
Bhlh Transcription Factor ◽  
Nucleotide Polymorphisms ◽  
Open Angle ◽  
Risk Alleles

AimTo validate six previously known primary open-angle glaucoma (POAG)-related loci in a Korean population.MethodsRepresentative POAG-related single-nucleotide polymorphisms (SNPs) from six loci (cyclin-dependent kinase 4 inhibitor B antisense RNA 1 (CDKN2B)-AS1, sineoculis homeobox homolog 1/sineoculis homeobox homolog 6(SIX1/SIX6), atonal BHLH transcription factor 7 (ATOH7), cell division cycle 7-transforming growth factor beta receptor 3, CAV1, transmembrane and coiled-coil domain family 1 (TMCO1) were selected and genotyped from discovery (POAG=309, heathy=5400) and replication cohorts (POAG=310, healthy=5612 and POAG=221, healthy=6244, respectively). Data were analysed using logistic regression to calculate the OR for POAG risk associated with SNP.ResultsFrom the discovery cohort, rs1900004 in ATOH7 (OR=1.29, p=0.0024); rs1063192 (OR=0.69, p=0.0006), rs2157719 (OR=0.63, p=0.0007) and rs7865618 (OR=0.63, p=0.0006) in CDKN2B-AS1, and rs10483727 in SIX1/SIX6 (OR=0.68, p=7.9E–05) were nominally associated with the risk of POAG. The replication cohorts revealed nominal associations with rs2157719 (OR=0.72, p=0.0135), rs1063192 (OR=0.63, p=0.0007) and rs7865618 (OR=0.52, p=0.0004) in CDKN2B-AS1. A mega-analysis from the entire Korean population revealed significance with rs1063192 (OR=0.77, p=6.0E–05), rs2157719 (OR=0.63, p=0.0007) and rs7865618 (OR=0.58, p=1.9E–06) in CDKN2B-AS1 and with rs10483727 in SIX1/SIX6 (OR=0.79, p=9.4E–05), with the same direction of effect between the discovery association and the replication sample.ConclusionsVariants near CDKN2B-AS1 and SIX1/SIX6 may require further investigation to obtain more genetic information on POAG development in a Korean population.

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