Displaying publications 1 - 20 of 42 in total

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  1. Agarwal R, Agarwal P
    Indian J Ophthalmol, 2012 Jul;60(4):255-61.
    PMID: 22824592 DOI: 10.4103/0301-4738.98700
    Glaucoma, a neurodegenerative disease, is currently being treated by modulation of one of its primary risk factors, the elevated intraocular pressure. Newer therapies that can provide direct neuroprotection to retinal ganglion cells are being extensively investigated. Tumor necrosis factor-α, a cytokine, has been recognized to play an important role in pro and antiapoptotic cellular events. In this paper we review the relevant literature to understand (1) The association of increased expression of tumor necrosis factor-α with glaucomatous neurodegeneraion, (2) Modulation of tumor necrosis factor-α expression by exposure to various risk factors of glaucoma, (3) Downstream cellular signaling mechanisms following interaction of tumor necrosis factor-α with its receptors and (4) Role of tumor necrosis factor-α as a possible target for therapeutic intervention in glaucoma. Literature was reviewed using PubMed search engine with relevant key words and a total of 82 English language papers published from 1990 to 2010 are included in this review.
  2. Agarwal R, Agarwal P
    Ophthalmic Res, 2010;43(1):1-10.
    PMID: 19829006 DOI: 10.1159/000246571
    Glaucoma, a leading cause of irreversible blindness, is often associated with increased resistance to aqueous outflow in trabecular tissue. Increased outflow resistance has been attributed to increased extracellular matrix (ECM) deposition in trabecular tissue. A critical balance between the synthesis and breakdown of the components of extracellular tissue is important in keeping the intraocular pressure within the normal range. Multiple mechanisms have been shown to affect ECM turnover in trabecular tissue. In this review, we examine the related literature to understand the role of TGF-beta in ECM turnover, in the development and progression of glaucoma, and in possible therapeutic strategies that can be devised by targeting the TGF-beta signaling pathways.
  3. Nekkanti S, Kaur K, Balagopal S, Agarwal P
    J Int Soc Prev Community Dent, 2020 11 24;10(6):759-765.
    PMID: 33437710 DOI: 10.4103/jispcd.JISPCD_339_20
    Aim and Objectives: Toothbrushing is one of the most important factors in controlling plaque accumulation and dental caries. There are vast varieties of toothbrushes available in the market. This study was designed to evaluate the effectiveness of novel chewable toothbrushes as compared to manual toothbrushes in plaque removal among 10-12-year-old children.

    Materials and Methods: This randomized controlled trial was conducted on 40 healthy children aged between 10 and 12 years of age who were randomly assigned to either of the groups: Group I--Chewable Toothbrushes and Group II--Manual Toothbrushes. Following oral prophylaxis, baseline records of oral hygiene indices (Simplified oral hygiene index (OHI-S) in indexed teeth and Turesky modification of Quigley Hein plaque index (TMQHI) were taken. Baseline Saliva samples were collected and sent for Streptococcus mutans counts. Children were then instructed to use their respective toothbrush twice daily for a week. Oral hygiene indices and S. mutans counts were repeated after 1 week.

    Results: Differences in pre-brushing and post-brushing plaque scores and salivary S. mutans counts were statistically significant when compared using paired-sample t test and independent-sample t test. There was a significant reduction in salivary S. mutans counts after using both chewable and manual toothbrushes. However, there was no statistically significant difference between the two groups (P = 0.08).

    Conclusion: Chewable toothbrushes are equally effective in plaque control when compared to manual toothbrushes. These can be a reliable alternative for children who lack manual dexterity.

  4. Agarwal R, Agarwal P
    Expert Opin Ther Targets, 2014 May;18(5):527-39.
    PMID: 24579961 DOI: 10.1517/14728222.2014.888416
    The homeostatic role of adenosine in regulating intraocular pressure (IOP) is now widely recognized, and hence, the drugs targeting adenosine receptors have become the focus of investigation. In this review, we summarize the adenosine receptor signaling pathways, which could be potential therapeutic targets for the management of glaucoma.
  5. Khalil H, Khalil M, Hashim I, Agarwal P
    Entropy (Basel), 2021 Sep 02;23(9).
    PMID: 34573779 DOI: 10.3390/e23091154
    We extend the operational matrices technique to design a spectral solution of nonlinear fractional differential equations (FDEs). The derivative is considered in the Caputo sense. The coupled system of two FDEs is considered, subjected to more generalized integral type conditions. The basis of our approach is the most simple orthogonal polynomials. Several new matrices are derived that have strong applications in the development of computational scheme. The scheme presented in this article is able to convert nonlinear coupled system of FDEs to an equivalent S-lvester type algebraic equation. The solution of the algebraic structure is constructed by converting the system into a complex Schur form. After conversion, the solution of the resultant triangular system is obtained and transformed back to construct the solution of algebraic structure. The solution of the matrix equation is used to construct the solution of the related nonlinear system of FDEs. The convergence of the proposed method is investigated analytically and verified experimentally through a wide variety of test problems.
  6. Agarwal R, Agarwal P
    Expert Opin Drug Discov, 2017 Mar;12(3):261-270.
    PMID: 28075618 DOI: 10.1080/17460441.2017.1281244
    Rodents have widely been used to represent glaucomatous changes both in the presence and absence of elevated intraocular pressure (IOP) as they offer clear advantages over other animal species. IOP elevation is commonly achieved by creating an obstruction in the aqueous outflow pathways, consequently leading to retinal ganglion cell and optic nerve (ON) damage, the hallmark of glaucoma. These changes may also be achieved in the absence of elevated IOP by directly inflicting injury to retina or ON. Areas covered: This paper presents a summary of currently used rodent models of glaucoma. The characteristics of these models from several studies are summarized. The benefits and shortcomings of these models are also discussed. Expert opinion: The choice of animal model that closely represents human disease is key for successful translational of preclinical research to clinical practice. Rodent models of rapid IOP elevation are likely to be least representative, whereas models such as steroid-induced glaucoma models more closely resemble the trabecular meshwork changes seen in glaucomatous human eyes. However, this model needs further characterization. Rodent models based on direct retinal and ON injury are also useful tools to investigate molecular mechanisms involved at the site of final common pathology and neuroprotective strategies.
  7. Agarwal R, Iezhitsa L, Agarwal P
    Biometals, 2013 Nov 15.
    PMID: 24233809
    Magnesium is one of the most important regulatory cation involved in several biological processes. It is important for maintaining the structural and functional integrity of several vital ocular tissues such as cornea, lens and retina. The magnesium content of lens, especially in its peripheral part, is higher than that in aqueous and vitreous humor. Magnesium has also been shown to play critically important role in retinal functions. Magnesium plays significant role as a cofactor for more than 350 enzymes in the body and regulates neuroexcitability and several ion channels. Membrane associated ATPase functions that are crucial in regulating the intracellular ionic environment, are magnesium-dependent. Moreover, the enzymes involved in ATP production and hydrolysis are also magnesium-dependent. Magnesium deficiency by interfering with ATPase functions causes increased intracellular calcium and sodium and decreases intracellular potassium concentration. Such ionic imbalances in turn alter the other cellular enzymatic reactions and form the basis of the association of magnesium deficiency with ophthalmic diseases such as cataract. In presence of magnesium deficiency, an imbalance between mediators of vasoconstriction and vasorelaxation may underlie the vasospasm, which is one of the pathogenic factors in primary open angle glaucoma. Furthermore, magnesium deficiency is also a contributing factor in increased oxidative stress and inducible NOS stimulation that can further contribute in the initiation and progression of ocular pathologies such as cataract, glaucoma and diabetic retinopathy. In this paper we review the association of disturbances of magnesium homeostasis with several ophthalmic diseases.
  8. Agarwal R, Agarwal P
    Exp Biol Med (Maywood), 2017 Feb;242(4):374-383.
    PMID: 27798117 DOI: 10.1177/1535370216675065
    Disturbances of extracellular matrix homeostasis are associated with a number of pathological conditions. The ability of extracellular matrix to provide contextual information and hence control the individual or collective cellular behavior is increasingly being recognized. Hence, newer therapeutic approaches targeting extracellular matrix remodeling are widely investigated. We reviewed the current literature showing the effects of resveratrol on various aspects of extracellular matrix remodeling. This review presents a summary of the effects of resveratrol on extracellular matrix deposition and breakdown. Mechanisms of action of resveratrol in extracellular matrix deposition involving growth factors and their signaling pathways are discussed. Involvement of phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways and role of transcription factors and sirtuins on the effects of resveratrol on extracellular matrix homeostasis are summarized. It is evident from the literature presented in this review that resveratrol has significant effects on both the synthesis and breakdown of extracellular matrix. The major molecular targets of the action of resveratrol are growth factors and their signaling pathways, phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways, transcription factors, and SIRT-1. The effects of resveratrol on extracellular matrix and the molecular targets appear to be related to experimental models, experimental environment as well as the doses.
  9. 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.
  10. Agarwal P, Agarwal R
    Expert Opin Ther Targets, 2021 Jul;25(7):585-596.
    PMID: 34402357 DOI: 10.1080/14728222.2021.1969362
    INTRODUCTION: The role of adenosine receptors as therapeutic targets for neuroprotection is now widely recognized. Their role, however, in protection against retinal ganglion cell (RGC) apoptosis in glaucoma needs further investigation. Hence, in this review, we look into the possibility of adenosine receptors as potential therapeutic targets by exploring their role in modulating various pathophysiological mechanisms underlying glaucomatous RGC loss.

    AREAS COVERED: This review presents a summary of the adenosine receptor distribution in retina and the cellular functions mediated by them. The major pathophysiological mechanisms such as excitotoxicity, vascular dysregulation, loss of neurotrophic signaling, and inflammatory responses involved in glaucomatous RGC loss are discussed. The literature showing the role of adenosine receptors in modulating these pathophysiological mechanisms is discussed. The literature search was conducted using Pubmed search engine using key words such as 'RGC apoptosis,' 'adenosine,' adenosine receptors' 'retina' 'excitotoxicity,' 'neurotrophins,' 'ischemia', and 'cytokines' individually and in various combinations.

    EXPERT OPINION: Use of adenosine receptor agonists and antagonists, for preservation of the RGCs in glaucomatous eyes independent of the level of intraocular pressure seems a very useful strategy. Future application of this strategy would require appropriate designing of drug formulation for tissue and disease-specific receptor targeting. Furthermore, the modulation of physiological functions and potential adverse effects need further investigations.

  11. 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.
  12. Agarwal R, Gupta SK, Srivastava S, Agarwal P, Agrawal SS
    Expert Opin Drug Discov, 2009 Feb;4(2):147-58.
    PMID: 23480513 DOI: 10.1517/13543770802668117
    Curcuma longa is among the most commonly used spices in India and other Asian countries. The herb has also been used in Ayurveda and other traditional systems of medicine for the prevention and treatment of a variety of ailments. Curcuminoids are the major chemical constituents of C. longa that are of medicinal importance. Today, a large body of scientific evidence exists to indicate potential therapeutic benefits of C. longa. Several preclinical and clinical studies have investigated the pharmacological properties of C. longa and results indicate strong therapeutic potential for anti-inflammatory, antioxidant, antibacterial, anticancer and many other properties.
  13. Seger S, Nasharuddin NNB, Fernandez SL, Yunus SRBM, Shun NTM, Agarwal P, et al.
    Pan Afr Med J, 2020;37:151.
    PMID: 33425184 DOI: 10.11604/pamj.2020.37.151.21716
    Introduction: irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorder. The medical programme is among the most challenging and stressful undergraduate programmes which may predispose to higher rates of IBS. This study sought to determine the prevalence of undiagnosed IBS and the factors associated with IBS among medical students in a Malaysian private university.

    Methods: a cross sectional study was conducted among the medical students from semester 6 to semester 9 (year 3, year 4 and year 5) of a Malaysian private university. The questionnaire consisted of 2 main sections. Section A was on demographic data and section B consisted of the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index (PSQI) and the Rome IV Questionnaire for IBS. Association between the factors gathered and IBS was assessed using the Chi-Square test. Variables with a p-value of less than 0.2 in the univariate analysis were entered into a multivariate analysis model.

    Results: number of students who responded were 190 (56.3%) were females, 66.3% were Chinese and 37.9% were from semester 9. Twenty-eight (14.7%) students had symptoms consistent with a diagnosis of IBS. Depression was found to be significantly associated with IBS (adjusted OR: 4.749, CI: 1.809-12.470).

    Conclusion: this study suggests that IBS is common among Malaysian medical students. There was a significant association between IBS and depression.

  14. Agarwal P, Wong YH, Das Gupta E, Agarwal R, Livingstone BI, Ramamurthy S, et al.
    Cutan Ocul Toxicol, 2015;34(3):179-84.
    PMID: 25068998 DOI: 10.3109/15569527.2014.938751
    BACKGROUND: Hydroxychloroquine (HCQ) is widely used for long-term treatment of autoimmune diseases such as rheumatoid arthritis. However, its long-term use is known to be associated with visual changes due to retinal damage. Retinal damage associated with long-term HCQ therapy is preventable if the drug is discontinued early when the patients are still asymptomatic. In view of contrasting reports from previous studies, we investigated the association of prolonged HCQ therapy with retinal thickness in macular area.
    METHODS: This study included 48 patients on long-term HCQ therapy and 38 healthy controls. All subjects underwent examination for corrected visual acuity, fundus photography, visual fields and SD-OCT for retinal thickness.
    RESULTS: Visual acuity, visual fields, fundus photography and SD-OCT did not reveal changes consistent with diagnosis of established HCQ retinopathy in any of the subjects from HCQ group. Retinal thickness in central, parafoveal and perifoveal areas did not show significant differences between HCQ and control groups. However, we observed negative correlation between cumulative dose and retinal thickness in the parafoveal (p = 0.003) and perifoveal areas (p = 0.019) but not in the central area.
    CONCLUSIONS: Correlation of cumulative dose with retinal thickness in parafoveal and perifoveal areas and not the central area is in accordance with the late appearance of HCQ-induced bull's eye retinopathy. Hence screening of asymptomatic patients using OCT seems to be of great importance for early detection of retinal changes.
    KEYWORDS: Cumulative dose; OCT; hydroxychloroquine; retinal thickness
  15. Agarwal R, Agarwal P, Iezhitsa I
    Expert Opin Drug Discov, 2023;18(11):1287-1300.
    PMID: 37608634 DOI: 10.1080/17460441.2023.2246892
    INTRODUCTION: Animal models are widely used in glaucoma-related research. Since the elevated intraocular pressure (IOP) is a major risk factor underlying the disease pathogenesis, animal models with high IOP are commonly used. However, models are also used to represent the clinical context of glaucomatous changes developing despite a normal IOP.

    AREAS COVERED: Herein, the authors discuss the various factors that contribute to the quality of studies using animal models based on the evaluation of studies published in 2022. The factors affecting the quality of studies using animal models, such as the animal species, age, and sex, are discussed, along with various methods and outcomes of studies involving different animal models of glaucoma.

    EXPERT OPINION: Translating animal research data to clinical applications remains challenging. Our observations in this review clearly indicate that many studies lack scientific robustness not only in their experiment conduct but also in data analysis, interpretation, and presentation. In this context, ensuring the internal validity of animal studies is the first step in quality assurance. External validity, however, is more challenging, and steps should be taken to satisfy external validity at least to some extent.

  16. Razali N, Agarwal R, Agarwal P, Kapitonova MY, Kannan Kutty M, Smirnov A, et al.
    Eur J Pharmacol, 2015 Feb 15;749:73-80.
    PMID: 25481859 DOI: 10.1016/j.ejphar.2014.11.029
    Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.
  17. Agarwal R, Iezhitsa I, Agarwal P, Abdul Nasir NA, Razali N, Alyautdin R, et al.
    Drug Deliv, 2016 May;23(4):1075-91.
    PMID: 25116511 DOI: 10.3109/10717544.2014.943336
    Topical route of administration is the most commonly used method for the treatment of ophthalmic diseases. However, presence of several layers of permeation barriers starting from the tear film till the inner layers of cornea make it difficult to achieve the therapeutic concentrations in the target tissue within the eye. In order to circumvent these barriers and to provide sustained and targeted drug delivery, tremendous advances have been made in developing efficient and safe drug delivery systems. Liposomes due to their unique structure prove to be extremely beneficial drug carriers as they can entrap both the hydrophilic and hydrophobic drugs. The conventional liposomes had several drawbacks particularly their tendency to aggregate, the instability and leakage of entrapped drug and susceptibility to phagocytosis. Due to this reason, for a long time, liposomes as drug delivery systems did not attract much attention of researchers and clinicians. However, over recent years development of new generation liposomes has opened up new approaches for targeted and sustained drug delivery using liposomes and has rejuvenated the interest of researchers in this field. In this review we present a summary of current literature to understand the anatomical and physiological limitation in achieving adequate ocular bioavailability of topically applied drugs and utility of liposomes in overcoming these limitations. The recent developments related to new generation liposomes are discussed.
  18. Razali N, Agarwal R, Agarwal P, Tripathy M, Kapitonova MY, Kutty MK, et al.
    Exp Eye Res, 2016 Feb;143:9-16.
    PMID: 26424219 DOI: 10.1016/j.exer.2015.09.014
    Steroid-induced hypertension and glaucoma is associated with increased extracellular meshwork (ECM) deposition in trabecular meshwork (TM). Previous studies have shown that single drop application of trans-resveratrol lowers IOP in steroid-induced ocular hypertensive (SIOH) rats. This IOP lowering is attributed to activation of adenosine A1 receptors, which may lead to increased matrix metalloproteinase (MMP)-2 activity. This study evaluated the effect of repeated topical application of trans-resveratrol for 21 days in SIOH animals on IOP, changes in MMP-2 level in aqueous humor, trabecular meshwork and retinal morphology and retinal redox status. We observed that treatment with trans-resveratrol results in significant and sustained IOP reduction in SIOH rats. This IOP reduction is associated with significantly higher aqueous humor total MMP-2 level; significantly reduced TM thickness and increased number of TM cells. Treatment with trans-resveratrol also significantly increased ganglion cell layer (GCL) thickness, the linear cell density in the GCL and inner retina thickness; and significantly reduced retinal oxidative stress compared to the SIOH vehicle-treated group. In conclusion, repeated dose topical application of trans-resveratrol produces sustained IOP lowering effect, which is associated with increased level of aqueous humor MMP-2, normalization of TM and retinal morphology and restoration of retinal redox status.
  19. Jafri AJA, Agarwal R, Iezhitsa I, Agarwal P, Ismail NM
    Amino Acids, 2019 Apr;51(4):641-646.
    PMID: 30656415 DOI: 10.1007/s00726-019-02696-4
    This study aimed to evaluate effect of TAU on NMDA-induced changes in retinal redox status, retinal cell apoptosis and retinal morphology in Sprague-Dawley rats. Taurine was injected intravitreally as pre-, co- or post-treatment with NMDA and 7 days post-treatment retinae were processed for estimation of oxidative stress, retinal morphology using H&E staining and retinal cell apoptosis using TUNEL staining. Treatment with TAU, particularly pre-treatment, significantly increased retinal glutathione, superoxide dismutase and catalase levels compared to NMDA-treated rats; whereas, the levels of malondialdehyde reduced significantly. Reduction in retinal oxidative stress in TAU pre-treated group was associated with significantly greater fractional thickness of ganglion cell layer within inner retina and retinal cell density in inner retina. TUNEL staining showed significantly reduced apoptotic cell count in TAU pre-treated group compared to NMDA group. It could be concluded that TAU protects against NMDA-induced retinal injury in rats by reducing retinal oxidative stress.
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