Kinin B1- and B2-Receptor Subtypes Contract Isolated Bovine Ciliary Muscle: Their Role in Ocular Lens Function and Intraocular Pressure Reduction.

Bradykinin is an endogenously produced nonapeptide with many physiological and pathological functions that are mediated by two pharmacologically defined receptor subtypes, B1- and B2-receptors. Current studies sought to characterize the functional bradykinin (BK) receptors present in freshly isolated bovine ciliary muscle (BCM) using an organ-bath tissue contraction system. Cumulative longitudinal isometric tension responses of BCM strips (4-5 mm) were recorded before and after the addition of test compounds to BCM strips hooked up to an isometric strain gauge transducer system.

Glutathione Modulates Hydrogen Sulfide Release and the Ocular Hypotensive Action of Diallyl Polysulfide Compounds.

Background: Hydrogen sulfide (HS) is an endogenous transmitter with the potential to regulate aqueous humor dynamics and protect retinal neurons from degeneration. The aim of the present study was two-fold: (a) to evaluate the release of HS from two polysulfides, diallyl disulfide (DADS), and diallyl trisulfide (DATS); and (b) to investigate their ocular hypotensive actions in normotensive male and female rabbits in the presence and absence of GSH.

Materials And Methods: HS was quantified hourly for up to 6 h using a HS-Biosensor (World Precision Instruments, Sarasota, Fl).

Neuroprotective Actions of Hydrogen Sulfide-Releasing Compounds in Isolated Bovine Retinae.

We have evidence that hydrogen sulfide (HS)-releasing compounds can reduce intraocular pressure in normotensive and glaucomatous rabbits by increasing the aqueous humor (AH) outflow through the trabecular meshwork. Since HS has been reported to possess neuroprotective actions, the prevention of retinal ganglion cell loss is an important strategy in the pharmacotherapy of glaucoma. Consequently, the present study aimed to investigate the neuroprotective actions of HS-releasing compounds against hydrogen peroxide (HO)-induced oxidative stress in an isolated bovine retina.

Roles of Prostaglandins and Hydrogen Sulfide in an Outflow Model of the Porcine Ocular Anterior Segment Ex Vivo.

Background: Hydrogen sulfide (HS)-releasing compounds can reduce intraocular pressure in normotensive rabbits by increasing aqueous humor (AH) outflow through the trabecular meshwork. In the present study, we investigated the contribution of endogenous HS and the role of intramurally generated prostaglandins in the observed increase in AH outflow facility in an ex vivo porcine ocular anterior segment model.

Material And Methods: Porcine ocular anterior segment explants were perfused with Dulbecco's Modified Eagle's Medium maintained at 37 °C and gassed with 5% CO and 95% air under an elevated pressure of 15 mmHg for four hours.

A critical insight into the physicochemical stability of macular carotenoids with respect to their industrial production, safety profile, targeted tissue delivery, and bioavailability.

Lutein, zeaxanthin, and mesozeaxanthin, collectively termed as macular pigments, are key carotenoids integral to optimized central vision of the eye. Therefore, nutraceuticals and functional foods have been developed commercially using carotenoid rich flowers, such as marigold and calendula or single celled photosynthetic algae, such as the Dunaliella. Industrial formulation of such products enriched in macular pigments have often suffered from serious bottlenecks in stability, delivery, and bioavailability.

Correction: Heruye et al. Current Trends in the Pharmacotherapy of Cataracts. 2020, , 15.

In the original publication [...

Current Insights on the Photoprotective Mechanism of the Macular Carotenoids, Lutein and Zeaxanthin: Safety, Efficacy and Bio-Delivery.

Ocular health has emerged as one of the major issues of global health concern with a decline in quality of life in an aging population, in particular and rise in the number of associated morbidities and mortalities. One of the chief reasons for vision impairment is oxidative damage inflicted to photoreceptors in rods and cone cells by blue light as well as UV radiation. The scenario has been aggravated by unprecedented rise in screen-time during the COVID and post-COVID era.

Development and application of LC-MS/MS method for the quantification of hydrogen sulfide in the eye.

There are limited studies that report the physiological levels of HS in the eye. The currently available UV/Vis methods lack the required sensitivity and precision. Hence, the purpose of this study was to develop and validate a sensitive and robust pre-column derivatization LC-MS/MS method to measure changes in HS levels in tissues from isolated porcine eyes.

Protective Action of Hydrogen Sulfide-Releasing Compounds against Oxidative Stress-Induced Cataract Formation in Cultured Bovine Lenses.

Purpose: The gaseous signalling molecule, hydrogen sulfide (HS) has antioxidant, anti-inflammatory and anti-apoptotic properties. Since oxidative stress has been implicated in the pathogenesis of cataracts and lenticular hydrogen peroxide (HO) is elevated in some cataract patients, the present study investigated the ability of HS-releasing compounds to prevent HO-induced cataract formation in cultured bovine lenses.

Methods: Lenses were cultured in either Dulbecco's Modified Eagle Medium (DMEM; control); HO (50 mM); ascorbic acid (AA; 3 mM) (positive control); and the HS-releasing compounds (diallyl trisulfide [DATS] or GYY4137) in the presence of HO (50 mM).

Interaction between hydrogen sulfide, nitric oxide, and carbon monoxide pathways in the bovine isolated retina.

Purpose: Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (HS) are physiologically relevant gaseous neurotransmitters that are endogenously produced in mammalian tissues. In the present study, we investigated the possibility that NO and CO can regulate the endogenous levels of HS in bovine isolated neural retina.

Methods: Isolated bovine neural retina were homogenized and tissue homogenates were treated with a NO synthase inhibitor, NO donor, heme oxygenase-1 inhibitor, and/donor.

Current Trends in the Pharmacotherapy of Cataracts.

Cataracts, one of the leading causes of preventable blindness worldwide, refers to lens degradation that is characterized by clouding, with consequent blurry vision. As life expectancies improve, the number of people affected with cataracts is predicted to increase worldwide, especially in low-income nations with limited access to surgery. Although cataract surgery is considered safe, it is associated with some complications such as retinal detachment, warranting a search for cheap, pharmacological alternatives to the management of this ocular disease.

Standardization of a new method for assessing the development of cataract in cultured bovine lenses.

Purpose: To standardize a new method for assessing cataractogenesis in isolated cultured bovine lenses using L-cysteine as the standard anti-cataract agent.

Methods: Intact bovine lenses were cultured in DMEM with L-cysteine in presence or absence of hydrogen peroxide (HO). Lens opacity (transmittance) was determined using a plate reader.

Hydrogen sulphide facilitates exocytosis by regulating the handling of intracellular calcium by chromaffin cells.

Gasotransmitter hydrogen sulphide (HS) has emerged as a regulator of multiple physiological and pathophysiological processes throughout. Here, we have investigated the effects of NaHS (fast donor of HS) and GYY4137 (GYY, slow donor of HS) on the exocytotic release of catecholamines from fast-perifused bovine adrenal chromaffin cells (BCCs) challenged with sequential intermittent pulses of a K-depolarizing solution. Both donors caused a concentration-dependent facilitation of secretion.

Pharmacology of Serotonin Receptors Causing Contraction of Isolated Bovine Posterior Ciliary Arteries: Role in Ocular Blood Flow.

Purpose: To determine the serotonergic (5HT) receptor subtype mediating the contraction of bovine posterior ciliary arteries (BPCAs) in vitro.

Methods: Longitudinal isometric tension was measured in BPCA strips (4-5 mm) mounted in 25 mL organ baths containing oxygenated Krebs solution at 37°C. Cumulative contractile concentration-response (C-R) curves were generated for various 5-HT agonists to assess their potencies and maximal degrees of contraction.

Serotonin-2B/2C Receptors Mediate Bovine Ciliary Muscle Contraction: Role in Intraocular Pressure Regulation.

Purpose: To study the pharmacological profile of the serotonin (5-hydroxytryptamine [5-HT]) receptor subtype mediating contractions in bovine isolated ciliary muscles.

Methods: Ciliary muscle strips were isolated from bovine eyeballs and mounted in organ baths containing aerated (95% O, 5% CO) Krebs buffer solution maintained at 37°C. Each muscle strip was attached at 1 end to a Grass Force-displacement Transducer connected to a Polyview Computer System for recording changes in isometric tension.

Comparative Effects of Hydrogen Sulfide-Releasing Compounds on [H]D-Aspartate Release from Bovine Isolated Retinae.

We investigated the pharmacological actions of a slow-releasing HS donor, GYY 4137; a substrate for the biosynthesis of HS, L-cysteine and its precursor, N-acetylcysteine on potassium (K; 50 mM)-evoked [H]D-aspartate release from bovine isolated retinae using the Superfusion Method. GYY 4137 (10 nM-10 µM), L-cysteine (100 nM-10 µM) and N-acetylcysteine (10 µM-1 mM) elicited a concentration-dependent decrease in K-evoked [H]D-aspartate release from isolated bovine retinae without affecting basal tritium efflux. At equimolar concentration of 10 µM, the rank order of activity was as follows: L-cysteine > GYY 4137 > N-acetylcysteine.

Regulation of Excitatory Amino Acid Transmission in the Retina: Studies on Neuroprotection.

Excitotoxicity occurs in neurons due to the accumulation of excitatory amino acids such as glutamate in the synaptic and extrasynaptic locations. In the retina, excessive glutamate concentrations trigger a neurotoxic cascade involving several mechanisms, including the elevation of intracellular calcium (Ca and the activation of α-amino-3-hydroxy 5-methyl-4-iso-xazole-propionic acid/kainate (AMPA/KA) and N-methyl-d-aspartate (NMDA) receptors leading to retinal degeneration. Both ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs) are present in the mammalian retina.

Regulation of Aqueous Humor Dynamics by Hydrogen Sulfide: Potential Role in Glaucoma Pharmacotherapy.

Hydrogen sulfide (HS) is a gaseous transmitter with well-known biological actions in a wide variety of tissues and organs. The potential involvement of this gas in physiological and pathological processes in the eye has led to several in vitro, ex vivo, and in vivo studies to understand its pharmacological role in some mammalian species. Evidence from literature demonstrates that 4 enzymes responsible for the biosynthesis of this gas (cystathionine β-synthase, CBS; cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3MST; and d-amino acid oxidase) are present in the cornea, iris, ciliary body, lens, and retina.

Effects of Hydrogen Sulfide-Releasing Compounds on Aqueous Humor Outflow Facility in Porcine Ocular Anterior Segments, Ex Vivo.

Purpose: To investigate the pharmacological actions of hydrogen sulfide (HS)-releasing compounds l-cysteine and sodium hydrosulfide (NaHS) on aqueous humor (AH) outflow facility in porcine ocular anterior segment.

Methods: Porcine ocular anterior segments were perfused with Dulbecco's modified Eagle's medium at a constant pressure of 7.35 mmHg.

Effect of Hydrogen Sulfide Donors on Intraocular Pressure in Rabbits.

Purpose: In this study, we investigated the effect of a slow-releasing hydrogen sulfide (H2S) donor, GYY 4137, on intraocular pressure (IOP) in normotensive rabbits. Furthermore, we compared the IOP-lowering action of GYY 4137 with those elicited by other H2S-producing compounds, l-cysteine and ACS67 (a hybrid compound of latanoprost with an H2S-releasing moiety).

Methods: IOP was measured in New Zealand normotensive male albino rabbits using a pneumatonometer (model 30 classic; Reichert Ophthalmic Instruments, Depew, NY).

Pharmacological Actions of Hydrogen Sulfide Donors on Sympathetic Neurotransmission in the Bovine Anterior Uvea, In Vitro.

In the present study, we investigated the effect of three different sources of hydrogen sulfide (H2S) on sympathetic neurotransmission from isolated superfused bovine iris-ciliary bodies. The three agents under consideration were: ACS67, a hybrid of latanoprost and a H2S-donating moiety; L-cysteine, a substrate for endogenous production of H2S and GYY 4137, a slow donor of H2S. We also examined the contribution of prostaglandins to the pharmacological actions of the H2S donors on release of [(3)H]-norepinephrine ([(3)H]NE) triggered by electrical field stimulation.

Inhibitory action of novel hydrogen sulfide donors on bovine isolated posterior ciliary arteries.

In the present study, we investigate the inhibitory effect of novel H2S donors, AP67 and AP72 on isolated bovine posterior ciliary arteries (PCAs) under conditions of tone induced by an adrenoceptor agonist. Furthermore, we examined the possible mechanisms underlying the AP67- and AP72-induced relaxations. Isolated bovine PCA were set up for measurement of isometric tension in organ baths containing oxygenated Krebs solution.

Role of the non-enzymatic metabolite of eicosapentaenoic acid, 5-epi-5-F3t-isoprostane in the regulation of [ (3)H]D-aspartate release in isolated bovine retina.

We have evidence that F2-isoprostanes (F2-IsoPs) regulate the release of excitatory neurotransmitters in isolated bovine retina. Although 5-F3-IsoPs are generated in mammals, in vivo, their pharmacological actions on neurotransmitter release remain unknown. In this study, we investigated the effect of 5-epi-5-F3t-IsoP on K(+)-evoked [(3)H]D-aspartate release in isolated bovine retina using the superfusion method.