Small RNA Sequencing Reveals a Distinct MicroRNA Signature between Glucocorticoid Responder and Glucocorticoid Non-Responder Primary Human Trabecular Meshwork Cells after Dexamethasone Treatment.

Glucocorticoids (GCs) are known to regulate several physiological processes and are the mainstay in the management of inflammatory eye diseases. The long-term use of GC causes raised intraocular pressure (IOP) or ocular hypertension (OHT) in about 30-50% of the susceptible individuals depending on the route of administration, and can lead to steroid-induced secondary glaucoma. The present study aims to understand the role of microRNAs (miRNAs) in differential glucocorticoid (GC) responsiveness in human trabecular meshwork (HTM) cells using small RNA sequencing.

Retinal Pigment Epithelium in Human Donor Eyes Contains Higher Levels of Bisretinoids Including A2E in Periphery than Macula.

Purpose: With age, human retinal pigment epithelium (RPE) accumulates bisretinoid fluorophores that may impact cellular function and contribute to age-related macular degeneration (AMD). Bisretinoids are comprised of a central pyridinium, dihydropyridinium, or cyclohexadiene ring. The pyridinium bisretinoid A2E has been extensively studied, and its quantity in the macula has been questioned.

A Comparative Genome-Wide Transcriptome Analysis of Glucocorticoid Responder and Non-Responder Primary Human Trabecular Meshwork Cells.

To investigate genes and pathways involved in differential glucocorticoid (GC) responsiveness in human trabecular meshwork (HTM) cells using RNA sequencing. Using paired human donor eyes, human organ-cultured anterior segment (HOCAS) was established in one eye to characterize GC responsiveness based on intra ocular pressure (IOP) change and, in the other eye, primary HTM cell culture was established. For RNA sequencing, total RNA extracted from GC-responder (GC-R) and non-responder (GC-NR) cells after dexamethasone (DEX) or ethanol (ETH) treatment for 7d was used.

Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro.

In the quest of identifying newer molecular targets for the management of glucocorticoid-induced ocular hypertension (GC-OHT) and glaucoma (GCG), several microarray studies have attempted to investigate the genome-wide transcriptome profiling of primary human trabecular meshwork (TM) cells in response to dexamethasone (DEX). However, no studies are reported so far to demonstrate the temporal changes in the expression of genes in the cultured human TM cells in response to DEX treatment. Therefore, in the present study, the time-dependent changes in the genome-wide expression of genes in primary human TM cells after short (16 hours: 16 h) and long exposure (7 days: 7 d) of DEX was investigated using RNA sequencing.

Inhibition of Aldose Reductase by Novel Phytocompounds: A Heuristic Approach to Treating Diabetic Retinopathy.

Aldose reductase (ALR2) activation in the polyol pathway has been implicated as the primary mechanism for the progression of diabetic retinopathy. Most of the aldose reductase inhibitors (ARIs), used for the treatment of diabetic complications, were withdrawn due to ineffective treatment and adverse side effects caused by nonspecificity. Epalrestat, a carboxylic acid inhibitor, is the only ARI used for the treatment of diabetic neuropathy, though associated with minor side effects to 8% of the treated population.

Incidence and risk factors for postoperative intraocular pressure response to topical prednisolone eye drops in patients undergoing phacoemulsification.

Aim/purpose: To report the incidence, risk factors, and magnitude of steroid response in individuals receiving topical 1% prednisolone acetate eye drops following phacoemulsification surgery MATERIALS AND METHODS: Postoperative IOP of 1118 consecutive patients who had uneventful cataract surgery and used 1% topical prednisolone acetate were studied. Baseline ocular parameters like best-corrected visual acuity, IOP, and slit-lamp examination findings were noted preoperatively and at postoperative day 30. Incidence of postoperative intraocular pressure response to steroid was analyzed and graded as mild, moderate, or severe and risk factors studied.

Drug reservoir function of voriconazole impregnated human amniotic membrane: An study.

Purpose: Earlier our group has demonstrated the drug reservoir function of the human amniotic membrane (HAM) using stable moxifloxacin and fortified cefazolin ophthalmic formulations and found it as a suitable tool to deliver drugs for an extended duration. The purpose of this study was to evaluate the extended-release kinetics of voriconazole from the impregnated human amniotic membrane (HAM) in vitro.

Methods: HAM buttons were incubated with freshly prepared 1% topical ophthalmic formulation of voriconazole for 5 different exposure time to investigate the ideal exposure time for the extended-release of voriconazole from HAM.

Assessment of differential intraocular pressure response to dexamethasone treatment in perfusion cultured Indian cadaveric eyes.

The purpose of the present study was to assess the differential intraocular pressure response (IOP) to dexamethasone (DEX) treatment at two dose levels (100 or 500 nM) in perfusion cultured Indian cadaveric eyes to investigate glucocorticoid (GC) responsiveness. In a human organ-cultured anterior segment (HOCAS) set-up, the eye pressure was monitored for every 24 h post DEX infusion (100 or 500 nM) or 0.1% ethanol treatment for 7 days after baseline stabilization.

SB772077B (SB77) Alleviated the Aqueous Outflow Resistance Mediated by Cyclic Mechanical Stress in Perfused Human Cadaveric Eyes.

The intraocular pressure lowering property of a new rho kinase inhibitor, SB772077B (SB77) has been previously demonstrated in perfused human cadaveric eyes. In this study, the efficacy of SB77 in alleviating the aqueous outflow resistance mediated by cyclic mechanical stress in perfused human cadaveric eyes was investigated. A human anterior segment perfusion culture model was used to investigate the effect of cyclic intraocular pressure (IOP) on aqueous outflow facility in presence or absence of SB77.

Human amniotic membrane as a drug carrier - An in-vitro study using fortified cefazolin ophthalmic solution.

Purpose: Our previous study demonstrated the drug reservoir function of human amniotic membrane (HAM) using stable moxifloxacin as a model drug. The purpose of the present study is to evaluate whether HAM can be used as a drug carrier for extended release of extemporaneous preparation of cefazolin.

Methods: HAM Buttons (1 Control, 5 Test) were incubated in a freshly prepared (1 ml) sterile topical solution of cefazolin 5% (w/v) for 3 h and 24 h at two different temperatures.

SB772077B, A New Rho Kinase Inhibitor Enhances Aqueous Humour Outflow Facility in Human Eyes.

We investigated the effect of a new Rho kinase inhibitor, SB772077B (SB77) on aqueous outflow facility (OF) in human eyes using human organ-cultured anterior segment (HOCAS). IOP was monitored for 24 h post-treatment with either SB77 (0.1/10/50 µM) or vehicle after a stable baseline pressure.

In Vitro Evaluation of the Drug Reservoir Function of Human Amniotic Membrane Using Moxifloxacin as a Model Drug.

Purpose: To evaluate the in vitro, extended drug reservoir function of human amniotic membrane (HAM) of different thicknesses impregnated with moxifloxacin.

Methods: HAM buttons (12 mm) were soaked with freshly prepared 0.5% wt/vol topical moxifloxacin at different soaking time intervals: 3 hours (group I), 6 hours (group II), 12 hours (group III), 24 hours (group IV), and 48 hours (group V).

Epalrestat, an Aldose Reductase Inhibitor Prevents Glucose-Induced Toxicity in Human Retinal Pigment Epithelial Cells In Vitro.

Purpose: Aldose reductase (ALR), the first and rate-limiting enzyme involved in polyol pathway plays a central role in diabetes and its related complications, including diabetic retinopathy (DR). Inhibition of ALR may also be an ideal target for reducing the deleterious effects of DR. Therefore, the purpose of the present study was to investigate the protective effect of epalrestat (EPL), ALR inhibitor on glucose-induced toxicity in ARPE-19 cells.

Identification of glaucomatous optic nerve head changes in Indian donor eyes without clinical history.

Purpose: The purpose of this study is to develop methods to identify glaucoma by examining the optic nerve head (ONH) of donor's eyes when information on the preexisting ocular disease is unavailable.

Materials And Methods: The ONH of the donor's eyes was evaluated under a stereomicroscope for the cup-disc ratio (CDR) and focal retinal rim thinning. The vertical diameter of the cup and disc was also measured using a precalibrated eyepiece micrometer.

Polymorphisms in sodium-dependent vitamin C transporter genes and plasma, aqueous humor and lens nucleus ascorbate concentrations in an ascorbate depleted setting.

We have previously reported low concentrations of plasma ascorbate and low dietary vitamin C intake in the older Indian population and a strong inverse association of these with cataract. Little is known about ascorbate levels in aqueous humor and lens in populations habitually depleted of ascorbate and no studies in any setting have investigated whether genetic polymorphisms influence ascorbate levels in ocular tissues. Our objectives were to investigate relationships between ascorbate concentrations in plasma, aqueous humor and lens and whether these relationships are influenced by Single Nucleotide Polymorphisms (SNPs) in sodium-dependent vitamin C transporter genes (SLC23A1 and SLC23A2).

Single and multidose ocular kinetics and stability analysis of extemporaneous formulation of topical voriconazole in humans.

Purpose: The purpose of the present study was to evaluate the kinetics of single and multiple doses of topical, non-preserved voriconazole (VZ) in human eyes.

Methods: For single dose kinetics, 119 patients undergoing cataract surgery were divided into group I and group II and each group received a single drop (30 µl) of either 1% or 0.1% VZ formulation.

Regional variation in the levels of macular xanthophylls and carotenoids in dietary components: comparing North and South India.

Multiple epidemiological studies have emphasized the intake of dark green leafy vegetables rich in xanthophylls in reducing the risk of developing age-related macular degeneration (AMD). Therefore, the present study was undertaken to quantify the levels of major carotenoids in commonly consumed fruits and vegetables of Indian origin and of xanthophylls in the macula of Indian human donor eyes. Fresh fruits (n=20) and vegetables (n=51) collected from two zones of India were tested for the estimation of xanthophyll, lycopene and β-carotene by using HPLC with Photodiode Array Detection.

Evidencing the modulation of P-glycoprotein at blood-ocular barriers using gamma scintigraphy.

Purpose: To evaluate the effect of P-glycoprotein modulation at blood-ocular barriers using gamma scintigraphy.

Methods: Ofloxacin, a fluoroquinolone, was selected as a substrate to study the drug efflux transporter (P-glycoprotein) modulation after labeling with Technetium ((99m)Tc) in rabbits. New Zealand albino rabbits were randomized into two groups of 4 each.

Evaluation of the impact of P-glycoprotein (P-gp) drug efflux transporter blockade on the systemic and ocular disposition of P-gp substrate.

Purpose: The impact of P-glycoprotein (P-gp) blockade on the intravenous (i.v.) pharmacokinetics of rhodamine-123 (Rho-123), and the subsequent effect on its disposition in ocular and nonocular tissues, was studied by using rabbits.

Evaluation of the modulation of P-glycoprotein (P-gp) on the intraocular disposition of its substrate in rabbits.

Purpose: To evaluate the functional role of P-gp and ocular tissue distribution of intravitreally injected Rhodamine-123 (Rho-123) in the presence of P-gp specific blocker (GF 120918) in normal as well as rifampicin-fed rabbits using microdialysis and direct sampling technique.

Methods: Intravitreal pharmacokinetics of Rho-123 were conducted in male New Zealand albino rabbits. Direct sampling and microdialysis were employed to study the disposition of Rho-123 in normal as well as rifampicin-fed conditions.