MyMedR

Displaying all 7 publications

Abstract:

Sort:

Triamterene measurements in the aqueous humor of rabbits

Hamid O, Tajuddin AA

J Ocul Pharmacol Ther, 2000 Dec;16(6):565-9.
PMID: 11132903

The kinetics of topical triamterene penetration were estimated from the time-course measurements of triamterene (in Dyazide) concentrations in the anterior chamber of six rabbits (n=12, left and right eyes). The two-compartment model of Jones and Maurice (1) was fitted to the measurements. We found the apparent elimination rate constant oftriamterene A = 0.33 +/- 0.12 hr(-1), the apparent absorption rate constant of triamterene B = 2.68 +/- 0.55 hr(-1), the cornea-aqueous transfer coefficient in reference to the corneal volume of triamterene kc.ca = 0.28 +/- 0.05 hr(-1), the loss coefficient of triamterene from the anterior chamber ko = 0.43 +/- 0.16 hr(-1) and the amount of triamterene in the cornea at time zero Mo = 483 +/- 125 ng/ml. The mean of ko = 0.43 hr(-1) is significantly lower (p = 0.04% using ZTEST) than the lower limit of aqueous loss coefficient = 0.58 hr(-1) usually found in rabbits (2). We conclude that Dyazide lowers the aqueous flow rate in the positive direction, considering glaucoma treatment. Peak triamterene concentration in the anterior chamber was P = 120 +/- 32 ng/ml. Half-life for elimination from the aqueous humor was T1/2 = 1.84 +/- 0.65 hr (Mean +/- SD).

Matched MeSH terms: Aqueous Humor/metabolism*
Advances in targeting the extracellular matrix for glaucoma therapy: current updates

Agarwal R, Iezhitsa I

Expert Opin Ther Targets, 2023;27(12):1217-1229.
PMID: 38069479 DOI: 10.1080/14728222.2023.2293748

INTRODUCTION: Elevated intraocular pressure (IOP) is a well-recognized risk factor for development of primary open angle glaucoma (POAG), a leading cause of irreversible blindness. Ocular hypertension is associated with excessive extracellular matrix (ECM) deposition in trabecular meshwork (TM) resulting in increased aqueous outflow resistance and elevated IOP. Hence, therapeutic options targeting ECM remodeling in TM to lower IOP in glaucomatous eyes are of considerable importance.
AREAS COVERED: This paper discusses the complex process of ECM regulation in TM and explores promising therapeutic targets. The role of Transforming Growth Factor-β as a central player in ECM deposition in TM is discussed. We elaborate the key regulatory processes involved in its activation, release, signaling, and cross talk with other signaling pathways including Rho GTPase, Wnt, integrin, cytokines, and renin-angiotensin-aldosterone. Further, we summarize the therapeutic agents that have been explored to target ECM dysregulation in TM.
EXPERT OPINION: Targeting molecular pathways to reduce ECM deposition and/or enhance its degradation are of considerable significance for IOP lowering. Challenges lie in pinpointing specific targets and designing drug delivery systems to precisely interact with pathologically active/inactive signaling. Recent advances in monoclonal antibodies, fusion molecules, and vectored nanotechnology offer potential solutions.

Matched MeSH terms: Aqueous Humor/metabolism
Fulltext Aqueous humor TGF-β2 levels in patients with open-angle glaucoma: A meta-analysis

Agarwal P, Daher AM, Agarwal R

Mol Vis, 2015;21:612-20.
PMID: 26019480

Elevated intraocular pressure (IOP) in glaucomatous eyes is often due to increased resistance to aqueous outflow. Previous studies have shown that increased extracellular material deposition in outflow pathways leads to increased resistance to aqueous outflow, and transforming growth factor (TGF)-β seems to play a role in the deposition of extracellular material. TGF-β2 is the predominant isoform in ocular tissue. Hence, comparison of the aqueous humor TGF-β2 level between patients with open-angle glaucoma (OAG) and controls would provide direct evidence for the role of TGF-β2 in the etiology of OAG. Hence, we performed this meta-analysis to develop an accurate estimate of the changes in aqueous humor TGF-β2 levels among OAG patients.

Matched MeSH terms: Aqueous Humor/metabolism*
Mechanisms of angiotensin converting enzyme inhibitor-induced IOP reduction in normotensive rats

Agarwal R, Krasilnikova AV, Raja IS, Agarwal P, Mohd Ismail N

Eur J Pharmacol, 2014 May 5;730:8-13.
PMID: 24583339 DOI: 10.1016/j.ejphar.2014.02.021

Angiotensin converting enzyme inhibitors (ACEIs) have been shown to lower intraocular pressure (IOP). Since, the ACEIs cause increased tissue prostaglandin levels, we hypothesized that the mechanisms of ACEI-induced IOP reduction have similarity with those of prostaglandin analogs. The present study investigated the involvement of matrix metalloproteinases (MMPs) and cytokine activity modulation as the underlying mechanisms of ACEI-induced ocular hypotension. The IOP lowering effect of single drop of enalaprilat dehydrate 1% was evaluated in rats pretreated with a broad spectrum MMP inhibitor or a cytokine inhibitor. Effect of angiotensin receptor blocker, losartan potassium 2%, was also studied to evaluate involvement of angiotensin II receptor type 1 (AT1) in IOP lowering effect of ACEI. Topical treatment with single drop of enalaprilat resulted in significant IOP reduction in treated eye with mean peak reduction 20.3% at 3h post-instillation. Treatment with losartan resulted in a peak IOP reduction of 13.3%, which was significantly lower than enalaprilat, indicating involvement of mechanisms in addition to AT1 blockade. Pretreatment with a broad spectrum MMP inhibitor or a cytokine inhibitor significantly attenuated the enalprilat-induced IOP reduction with mean peak IOP reduction of 11.2% and 13.6% respectively. The IOP-lowering effect of enalaprilat seems to be attributed to reduced angiotensin II type 1 receptor stimulation and modulation of MMP and cytokines activities.

Matched MeSH terms: Aqueous Humor/metabolism
Fulltext Matrix metalloproteinases and tissue inhibitors of metalloproteinases in the aqueous humour of patients with primary angle closure glaucoma - a quantitative study

Nga AD, Yap SL, Samsudin A, Abdul-Rahman PS, Hashim OH, Mimiwati Z

BMC Ophthalmol, 2014;14:33.
PMID: 24655889 DOI: 10.1186/1471-2415-14-33

Altered levels of specific matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the aqueous humour of primary open-angle glaucoma (POAG) eyes have been described. In this study, levels of specific MMPs and TIMPs in the aqueous humour of primary angle-closure glaucoma (PACG) eyes were measured and compared with those of POAG as well as non-glaucoma control eyes.

Matched MeSH terms: Aqueous Humor/metabolism*
Trabecular meshwork ECM remodeling in glaucoma: could RAS be a target?

Agarwal P, Agarwal R

Expert Opin Ther Targets, 2018 07;22(7):629-638.
PMID: 29883239 DOI: 10.1080/14728222.2018.1486822

INTRODUCTION: Disturbances of extracellular matrix (ECM) homeostasis in trabecular meshwork (TM) cause increased aqueous outflow resistance leading to elevated intraocular pressure (IOP) in glaucomatous eyes. Therefore, restoration of ECM homeostasis is a rational approach to prevent disease progression. Since renin-angiotensin system (RAS) inhibition positively alters ECM homeostasis in cardiovascular pathologies involving pressure and volume overload, it is likely that RAS inhibitors reduce IOP primarily by restoring ECM homeostasis. Areas covered: Current evidence showing the presence of RAS components in ocular tissue and its role in regulating aqueous humor dynamics is briefly summarized. The role of RAS in ECM remodeling is discussed both in terms of its effects on ECM synthesis and its breakdown. The mechanisms of ECM remodeling involving interactions of RAS with transforming growth factor-β, Wnt/β-catenin signaling, bone morphogenic proteins, connective tissue growth factor, and matrix metalloproteinases in ocular tissue are discussed. Expert opinion: Current literature strongly indicates a significant role of RAS in ECM remodeling in TM of hypertensive eyes. Hence, IOP-lowering effect of RAS inhibitors may primarily be attributed to restoration of ECM homeostasis in aqueous outflow pathways rather than its vascular effects. However, the mechanistic targets for RAS inhibitors have much wider distribution and consequences, which remain relatively unexplored in TM.

Matched MeSH terms: Aqueous Humor/metabolism
Plasma, aqueous and vitreous homocysteine levels in proliferative diabetic retinopathy

Lim CP, Loo AV, Khaw KW, Sthaneshwar P, Khang TF, Hassan M, et al.

Br J Ophthalmol, 2012 May;96(5):704-7.
PMID: 22353698 DOI: 10.1136/bjophthalmol-2011-301044

To compare homocysteine (Hcy) concentration in the blood plasma, vitreous and aqueous of eyes with proliferative diabetic retinopathy (PDR) against control, and to investigate associations between Hcy concentration in blood plasma with that of aqueous and vitreous in these two groups.

Matched MeSH terms: Aqueous Humor/metabolism*