Ocular Hypotensive Effect Research Articles

Subconjunctival Administration of an Adeno-Associated Virus Expressing Stanniocalcin-1 Provides Sustained Intraocular Pressure Reduction in Mice

PurposeTo investigate subconjunctival administration of a single-stranded, adeno-associated virus, serotype 2, engineered to express Stanniocalcin-1 with a FLAG tag (ssAAV2-STC-1-FLAG) as a novel sustained intraocular pressure (IOP) lowering agent with a reduced ocular surface side effect profile. DesignIn vivo pre-clinical investigation in mice SubjectsC57BL/6J, DBA/2J, FP receptor knockout mice MethodsNormotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 μL; 6 x 109 viral genomes [VGs]) in one eye and the same volume and concentration of ssAAV2-GFP or the same volume of PBS in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 x 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Steroid-mediated ocular hypertension was induced in C57BL/6J mice with weekly injections of dexamethasone into the conjunctival fornix, and mice were then injected subconjunctivally with 6 x 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. FP receptor knockout mice were injected subconjunctivally with 6 x 109 VGs of ssAAV2-STC-1-FLAG or PBS. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. IOP was assessed using the Tonolab tonometer for all experiments. Tumor necrosis factor alpha (TNFα), a marker of ocular surface inflammation, was compared between subconjunctivally delivered ssAAV2-STC-1 and other treatments including daily topical latanoprost. Main outcome measuresIOP assessment ResultsSubconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 2 post injection (17.4%; 17.1 ± 0.8 vs 14.1 ± 0.8 mmHg, P<0.001). After the IOP-lowering effect had waned, a second injection restored the ocular hypotensive effect. Subconjunctivally delivered ssAAV2-STC-1-FLAG lowered IOP in DBA/2J mice (16.9%; 17.8 ± 2.0 vs 14.8 ± 0.9 mmHg, P<0.001) and steroid-mediated ocular hypertensive mice (19.4%; 18.7 ±0.9 vs 15.1 ± 0.5 mmHg, P<0.001) over the experimental period. This construct also reduced IOP to a similar extent in wild type (15.9%) and FP receptor knockout (15.7%) mice compared to the fellow eye. A related construct also lowered IOP without the FLAG tag in a similar manner. Reduction in conjunctival TNFα was seen when comparing subconjunctivally delivered ssAAV2-STC-1-FLAG to daily topical latanoprost. ConclusionsSubconjunctival delivery of the STC-1 transgene with a vector system may represent a novel treatment strategy for sustained IOP reduction and improved ocular tolerability that also avoids the daily dosing requirements of currently available medications.

Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents

The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2% w/v) and the osmoprotectants betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34 nm) and a zeta potential of -13.96 ± 0.78 mV. LAT-HA-LIP was isotonic (284.00 ± 1.41 mOsm L−1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70 mN m−1) and viscosity (2.69 ± 0.15 mPa s−1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24 h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.Graphical abstract

Effect of nadolol in treatment of induced ocular hypertension in rabbits

In glaucoma, as optic neuropathy gradually proceeds unnoticed by the patient, early detection and treatment is of paramount importance in arresting or controlling the progress of damage. To explore effects of topical nadolol on intraocular pressure (IOP) ocular hypertensive eyes of rabbits. A group of 36 males of the rabbits were included in this study. Induction of ocular hypertension was achieved by injection of hydroxy propyl methylcellulose in the anterior chamber of rabbits right eye. The present study was designed to evaluate the possible beneficial therapeutic effect. The included rabbits were divided into distilled water group, timolol (0.25% and 0.5%) groups, and nadolol (0.25% and 0.5%). Each of drug eye drops (including distilled water) were instilled into right eyes 3 times/day for 10 days therapeutically. The rabbits had been examined for the IOP, pupil diameter, light reflex, corneal reflex, and conjunctival redness prior to instillation of drugs and along the trial period. Results: Ocular hypotensive effects of nadolol (0.25%) and (0.5%) eye drops were more efficient than that of distilled water (P&lt;0.01). Furthermore, nadolol eye drop was more efficient than timolol eye drop (0.01&gt;P&gt;0.05) in its ocular hypotensive effect in both concentrations along the trial period. In both parts of the present study and regarding each of mean pupil diameter, light reflex, corneal reflex and conjunctival redness, nadolol (0.25% or 0.5%) eye drops had no significant adverse effect (P &gt; 0.05). Conclusions: Nadolol eye drops instilled 3 times / day had an obvious beneficial, safe, and tolerable therapeutic ocular hypotensive effects on hydroxy propyl methyl cellulose - induced ocular hypertension in rabbits.

Bimatoprost Ophthalmic Solution (BOS) 0.3 mg w/v for 1 Open Trial of Long-term Preventive Therapy of Migraine in 3 patients with Pathophysiologic Shift from Brain to Eye

Known since antiquity, migraine is a complex primary disorder, an episodic painful Autonomic Nervous System (ANS) storm, generally following the stress/post-stress phase. Despite exhaustive study of neuropeptides, neurochemicals, molecules, neurogenetics, neuroimaging along with animal and human experiments over the last 50 years, the scientific basis of migraine remains unknown. Straddling eight decades from Cortical Spreading Depression (CSD) to Calcitonin-Gene Related Peptide (CGRP) and its antagonists, exponentially increasing data have failed to create a gestalt synthesis. This article lays cohesive and robust fundamental principles for the comprehension and management of migraine. The continuum between migraine and non-congestive Primary Open-Angle Glaucoma (POAG), Normal Tension Glaucoma (NTG), or Low-Tension Glaucoma (LTG) is advancing. The case of sustained remission of migraine attacks (&gt; 75%) over 3 years - 5 years with ocular hypotensive topical Bimatoprost Ophthalmic Solution (BOS) 0.3% in an N-of-1 trial in 3 patients with refractory migraine is presented. A cause-effect-adaptive process underlies the ANS-stress/post-stress-linked biology of migraine. Vasopressin-serotonin-norepinephrine ‘homeostatic-adaptive system’ Lowers Intraocular Pressure (IOP), while enhancing anti-stress, antinociception, vasomotor, and behaviour control functions, thereby selectively decreasing algogenic neural traffic in the ophthalmic division of trigeminal nerve (V1), and, raising the threshold to develop migraine. Striking migraine headache-aborting feature of vomiting is also likely linked to a several hundred-fold increase in arginine-vasopressin secretion. Eye-cover tests and self-ocular digital displacement are essential to studying the visual aura. Real-time physical displacement of Scintillating Scotoma (SS) and floating ‘stars’ is reported. The basis of spontaneous onset and offset, self-limited duration of migraine attacks, as well as female preponderance, and age/menopause decline in prevalence, are elucidated. Intraocular implants with long-term ocular hypotensive effects, including bimatoprost, are the future of migraine management. Controlled trials are required to establish the migraine-preventive effect of topical bimatoprost, a revolutionary advance in neuroscience.

Ocular hypotensive effect of fermented Pentaclethra macrophylla seeds in experimentally-induced glaucoma

ABSTRACT The study aimed to investigate the effect of fermented n-hexane extract of Pentaclethra macrophylla seeds (FPMSE) in an experimental model of glaucoma. Eighteen rabbits (1-1.8 kg body weight) were allocated into six groups of three rabbits (six eyes per group). Group 1 was the normal control. Ocular hypertension was induced with 1% prednisolone acetate ophthalmic solution in groups 2-6, twice daily for 21 days. Group 2 received no treatment, while groups 3–6 received 5 mg/kg b.w. acetazolamide, 100, 200, and 300 mg/kg b.w. extract, respectively. The intraocular pressures and other biochemical parameters were evaluated. The existence of bioactive compounds was determined via phytochemical analysis. Compared to group 2, the administration of FPMSE resulted in a significant decrease in IOP in the treated groups. Malondialdehyde concentrations in the treated groups’ aqueous humor and plasma were considerably lower (p < 0.05) than in group 2. Compared to group 2, glutathione, nitric oxide, and antioxidant levels improved significantly (p < 0.05). C-reactive protein and glutamate levels in group 2 were comparable (p > 0.05). FPMSE substantially reduced phospholipase A2 activity. Histological assessment of the ciliary body showed adequate pigmentations in the treatment groups compared to group 2. Hence, FPMSE possesses ocular hypotensive effects.

Comparison of tube shunt implantation and trabeculectomy for glaucoma: a systematic review and meta-analysis

ObjectiveTo compare the efficacy and safety of tube shunt implantation with trabeculectomy in the treatment of patients with glaucoma.MethodsA systematic literature search was performed for studies comparing tube with trabeculectomy...

CB1R, CB2R and TRPV1 expression and modulation in in vivo, animal glaucoma models: A systematic review.

The endocannabinoid system (ECS) is a complex biological regulatory system. Its expression and functionality have been widely investigated in ocular tissues. Recent data have reported its modulation to be valid in determining an ocular hypotensive and a neuroprotective effect in preclinical animal models of glaucoma. This study aimed to explore the available literature on cannabinoid receptor 1 (CB1R), cannabinoid receptor 2 (CB2R), and transient receptor potential vanilloid 1 (TRPV1) expression in the trabecular meshwork (TM), ciliary body (CB), and retina as well as their ocular hypotensive and neuroprotective effects in preclinical, in vivo, animal glaucoma models. The study adhered to both PRISMA and SYRCLE guidelines. Sixty-nine full-length articles were included in the final analysis. Preclinical studies indicated a widespread distribution of CB1R, CB2R, and TRPV1 in the TM, CB, and retina, although receptor-, age-, and species-dependent differences were observed. CB1R and CB2R modulation have been shown to exert ocular hypotensive effects in preclinical models via the regulation of inflow and outflow pathways. Retinal cell neuroprotection has been achieved in several experimental models, mediated by agonists and antagonists of CB1R, CB2R, and TRPV1. Despite the growing body of preclinical data regarding the expression and modulation of ECS in ocular tissues, the mechanisms responsible for the hypotensive and neuroprotective efficacy exerted by this system remain largely elusive. Research on this topic is advocated to further substantiate the hypothesis that the ECS is a new potential therapeutic target in the context of glaucoma.

Ocular Hypotensive Effects of Sacubitril and Valsartan Eye Drops on Ocular Normotensive and Betamethasone-Induced Ocular Hypertensive Rabbits

Ocular Hypotensive Effects of Sacubitril and Valsartan Eye Drops on Ocular Normotensive and Betamethasone-Induced Ocular Hypertensive Rabbits

Magnesium Hydroxide Nanoparticles Improve the Ocular Hypotensive Effect of Twice Daily Topical Timolol Maleate in Healthy Dogs.

Timolol maleate (TM), a beta-adrenergic receptor antagonist, is widely used for canine antiglaucoma eye drops; however, its bioavailability is <5%. Our previous study revealed that magnesium hydroxide nanoparticles (nMH) have potency in improving the bioavailability of fixed-combined TM in rodent models. This study aimed to investigate whether the fixed combination with nMH improves the ocular hypotensive effect of TM and affects pupil size (PS), heart rate (HR), and mean arterial pressure (MAP) in clinically healthy dogs. Five clinically healthy dogs were administered topical saline, commercial 0.5% TM, and a 0.01% or 0.1% nMH–0.5% TM fixed combination (0.01% or 0.1% nMH–TM) twice daily in one eye for 7 days with at least a 28-day interval. The changes from baseline were calculated and were statistically analyzed for each drug. IOP was significantly reduced in both 0.01% and 0.1% nMH–TM-treated-dogs compared with saline- and TM-treated dogs. Meanwhile, 0.01% and 0.1% nMH did not exacerbate the side effects of TM. From these results, nMH improved the ocular hypotensive effect of TM without enhancing side effects. Topical nMH–TM is potentially more effective for canine ocular hypotensive eye drops than TM.

Calcium-Phosphate Nanoparticles — a System for Drug Delivery to the Anterior Eye Chamber

Purpose: to prepare and characterize calcium-phosphate nanoparticles loaded with compounds of different nature: low-molecular inhibitor of angiotensin-converting enzyme lisinopril, and high-molecular enzyme superoxide dismutase 1. To estimate the possibility of enhancing the biological efficacy of these compounds via incorporation to the nanoparticles.Material and methods. To increase the stability of calcium-phosphate nanoparticles coating with β-D-cellobiose was used. The size, surface charge (ζ-potential) of the particles and efficacy of including of the selected compounds to the particles were measured. Comparative assessment of the efficacy of lisinopril solution and lisinopril in nanoparticles was made via the estimation of their ocular hypotensive effect in normotensive rabbits. To compare the efficacy of the superoxide dismutase 1 solution and superoxide dismutase 1 in nanoparticles the rabbit model of immunogenic uveitis was used. We estimated the clinical score for several signs of uveitis, protein level, and antioxidant activity in aqueous humor.Results. Calcium-phosphate nanoparticles containing lisinopril had average hydrodynamic radius of 170–300 nm and negative ζ-potential of –17 mV. Particles containing superoxide dismutase 1 had average hydrodynamic radius of 220–450 nm and negative ζ-potential of –4 mV. Lisinopril in nanoparticles caused a significantly greater decrease of intraocular pressure than lisinopril solution. Superoxide dismutase 1 in calcium-phosphate nanoparticles more efficiently decreased the clinical manifestations of uveitis and normalized the biochemical processes in aqueous humor than the enzyme in buffer solution.Conclusion. Incorporation of both low-molecular and high-molecular drugs to the calcium-phosphate nanoparticles enhance their bioavailability and therapeutic efficiency. The data obtained give evidence of the prospectively of the using of these nanoparticles as vehicles for the ophthalmic drugs used in eyedrops.

Pharmacological Profile and Ocular Hypotensive Effects of Cromakalim Prodrug 1, a Novel ATP-Sensitive Potassium Channel Opener, in Normotensive Dogs and Nonhuman Primates.

Purpose: To evaluate pharmacokinetic parameters and ocular hypotensive effects of cromakalim prodrug 1 (CKLP1) in normotensive large animal models. Methods: Optimal CKLP1 concentration was determined by dose response and utilized in short- (5-8 days) and long-term (60 days) evaluation in hound dogs (n = 5) and African Green Monkeys (n = 5). Blood pressure was recorded 3-5 times per week with a tail cuff. Concentrations of CKLP1 and the parent compound levcromakalim were assessed in hound dog plasma and select tissues by LC-MS/MS after bilateral ocular treatment with CKLP1 for 8 days. Pharmacokinetic parameters were calculated from days 1, 4, and 8 data. After necropsy, histology was assessed in 43 tissue samples from each animal. Results: In hound dogs and African Green monkeys, 10 mM CKLP1 (optimal concentration) significantly lowered intraocular pressure (IOP) by 18.9% ± 1.1% and 16.7% ± 6.7%, respectively, compared with control eyes (P < 0.05). During treatment, no significant change in systolic or diastolic blood pressure was observed in either species (P > 0.1). Average values for half-life of CKLP1 was 295.3 ± 140.4 min, Cmax, 10.5 ± 1.6 ng/mL, and area under the concentration vs. time curve (AUClast) 5261.4 ± 918.9 ng·min/mL. For levcromakalim, average values of half-life were 96.2 ± 27 min, Cmax 1.2 ± 0.2 ng/mL, and AUClast 281.2 ± 110.8 ng·min/mL. No significant pathology was identified. Conclusions: CKLP1 lowered IOP in hound dogs and African green monkeys with no effect on systemic blood pressure. Ocular topical treatment of CKLP1 showed excellent tolerability even after extended treatment periods.

EFFICACY OF CYCLOCRYOTHERAPY AND TRANSSCLERAL DIODE LASER CYCLOPHOTOCOAGULATION IN THE MANAGEMENT OF REFRACTORY GLAUCOMA.

SUMMARYTreating advanced glaucoma often requires numerous therapeutic modalities in order to achieve the desired intraocular pressure (IOP) reduction. The purpose of this study was to evaluate the IOP lowering efficacy of both cyclocryotherapy (CCT) and transscleral diode laser cyclophotocoagulation (TS-DCPC) in the management of refractory primary open-angle glaucoma. This prospective, randomized, controlled clinical trial included 40 patients (40 eyes) with refractory glaucoma treated at the Eye Department, Clinical Center of Vojvodina, Novi Sad, Serbia, between January 2016 and June 2019. Twenty patients underwent CCT (group 1), while another twenty patients were treated with TS-DCPC (group 2). Each patient underwent complete eye examination on the treatment day, as well as follow-up eye examinations 7 days and 1, 6 and 12 months after the intervention, when IOP and number of anti-glaucoma drugs used were recorded. The median baseline IOP was 36.50 mm Hg (IQR, 28.75-42.00) in group 1 and 27.00 mm Hg (IQR, 22.00-35.00) in group 2. Follow-up measurements of IOP in group 1 showed the following results: 16.50 mm Hg (IQR, 7.75-20.00) (60% decrease from the baseline value), 12.00 mm Hg (IQR, 9.25-18.00) (67% decrease from the baseline value), 9.00 mm Hg (IQR, 2.00-13.75) (73% decrease from the baseline value), and 9.50 (IQR, 2.50-12.00) (75% decrease from the baseline value) after 7 days, 1, 6 and 12 months, respectively. Follow-up measurements of IOP in group 2 showed the following results: 16.00 mm Hg (IQR, 10.00-17.00) (48% decrease from the baseline value), 14.00 mm Hg (IQR, 10.00-16.00) (56% decrease from the baseline value), 14.00 mm Hg (IQR, 12.25-16.50) (43% decrease from the baseline value) and 14.00 mm Hg (IQR, 11.25-15.75) (53% decrease from the baseline value) after 7 days, 1, 6 and 12 months, respectively. The mean number of antiglaucoma drugs used decreased from 4 to 0.65±0.81 and 2.25±1.07 in groups 1 and 2, respectively. In conclusion, study results confirmed the CCT and TS-DCPC to have a rapid and statistically significant ocular hypotensive effect in eyes with refractory glaucoma at one-year follow-up.

Combined Trabeculotomy-Trabeculectomy Versus Trabeculectomy for Treatment of Silicone Oil-induced Ocular Hypertension.

Combined trabeculotomy-trabeculectomy (CTT) has a significantly better hypotensive effect than trabeculectomy and a higher success rate in cases of silicone oil-induced ocular hypertension. To compare the ocular hypotensive effect of CTT with mitomycin-C (MMC) to that of trabeculectomy with MMC in cases of silicone oil-induced ocular hypertension. Thirty eyes of 30 patients with high intraocular pressure (IOP) after vitrectomy and silicone oil injection (followed by silicone oil removal) were randomly allocated to 2 groups in this randomized trial. Group A was composed of 15 cases who underwent combined CTT with MMC while group B cases contained 15 cases undergoing trabeculectomy with MMC. Patients were followed up for 12 months. We included patients above 18 years old, having performed vitrectomy and silicone oil injection followed by oil removal, and having IOP >21 mm Hg uncontrollable by antiglaucoma medications. The postoperative IOP drop was significantly greater in group A than in group B at all follow up visits (P<0.05). Compared with preoperative IOP, both surgeries produced a significantly lower postoperative IOP at all follow-up visits (P<0.05). For group A, complete success rates (IOP≤21 mm Hg without ocular hypotensive medications) and qualified success rates (IOP≤21 mm Hg with or without ocular hypotensive medications) were both higher than for group B. Both surgeries effectively reduce IOP in cases of silicone oil-induced ocular hypertension, but CTT has a significantly better hypotensive effect and a higher success rate on the long-term.

Polypeptide and glycosaminoglycan polysaccharide as stabilizing polymers in nanocrystals for a safe ocular hypotensive effect

Improved ocular delivery of a poorly soluble anti-glaucoma drug, acetazolamide (ACZ), in a stable nanosuspension (NS) was the main target of the study. The anionic polypeptide, poly-γ-glutamic acid (PG) and the glycosaminoglycan, hyaluronic acid, were used to stabilize ACZ-NS prepared using the antisolvent precipitation (AS-PT) coupled with sonication technique. To endue in site biocompatibility with high tolerability, soya lecithin (SL) phospholipid has been also combined with polyvinyl alcohol (PVA). NS with uniform PS in the range 100–300 nm, high ζ > ±20 mV, and enhanced saturation solubility were produced. Targeting solvent removal with control on future particle growth, post-production processing of NS was done using spray drying. The carriers' composition and amount relative to ACZ-NS were optimized to allow for the production of a redispersible dry crystalline powder. Particles crystallinity was confirmed using X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) in liquid and spray dried NS. The modified Draize test proved the safety and tolerability following application to rabbit eyes accompanying an efficient ocular hypotensive activity using a steroid glaucoma model.

Effect of the chemical structure on the drug release from brinzolamide based nano eye-drops

Commercially available eye-drops scarcely penetrate the eye because of the cornea, which is located at the surface of the eye and function of barrier to keep out foreign matter. To enhance the penetration ratio of eye-drop, we have proposed nanometer-sized eye-drops called “nano eye-drops.” A series of prodrug compounds derived from brinzolamide, a glaucoma therapeutic agent, connected with a trimethyl lock (TML) group were synthesized and the nano eye-drops of the resulting prodrugs were successfully fabricated by the reprecipitation method. We found that the drug release of nano eye-drops critically depended on the chemical structure of the prodrugs comprising the nano eye-drops. As a result, the timing of the ocular hypotensive effect was controlled by altering the chemical structure of brinzolamide prodrug. These results provide insight into drug design for effective controlled release.

Low-dose Bevacizumab Decreases Ocular Hypotensive Effect of Angiotensin II in Sprague Dawley Rats

ABSTRACT Purpose Although the effectiveness of anti-VEGF agents in ophthalmology has been thoroughly documented, we do not fully comprehend the epidemiology and mechanistic background of their side effects, including intraocular and systemic hypertension. Here, we investigate the interference of a low-dose bevacizumab with key neuronal and humoral mechanisms maintaining blood and intraocular pressure homeostasis. Materials and methods Intraocular pressure (IOP), blood pressure (BP), and heart rate (HR) were measured in SPRD rats pretreated with bevacizumab or 0.9% NaCl at baseline and after infusion of angiotensin II, a humoral mediator involved in BP and IOP regulation. Superior cervical gangliectomy was performed to assess the effect of sympathetic nervous system on the analyzed parameters. Additionally, we studied the expression of a subset of genes related to renin-angiotensin system in the anterior segment of the eye. Results At baseline, there was no significant difference in IOP, BP, and HR between rats pretreated with 0.9% NaCl and bevacizumab. Infusion of angiotensin II lowered IOP in rats pretreated with 0.9% NaCl, but not in rats pretreated with bevacizumab (30 min: ∆4.22 ± 1.2 vs. baseline, p > .05; ∆0.83 ± 0.66 vs. baseline, p < .05) This effect was paralleled by an increased expression of angiotensin II type 1b and type 2 receptors in the anterior segment of the eye (AT1b: 1 ± 0.65 vs 7.35 ± 2.84, p < .05; AT2: 1 ± 0.05 vs. 12.8 ± 0.1, p < .05). Angiotensin II infusion increased BP in both groups (10 min: bevacizumab ∆44.6 ± 3.2, p < .05; 0.9%NaCl ∆37.1 ± 5.1, p < .05), whereas did not have any effect on HR. Sympathetic ocular denervation did not affect any of the analyzed parameters. Conclusions We found that low-dose bevacizumab interferes with IOP-lowering properties of angiotensin II. This effect might be related to increased expression of angiotensin II receptors in the anterior segment of the eye.

Data on differentially expressed proteins in rock inhibitor-treated human trabecular meshwork cells using SWATH-based proteomics.

Rho-associated coiled coil-forming protein kinase (ROCK) inhibitors represent a novel class of anti-glaucoma drugs because of their ocular hypotensive effects. However, the underlying mechanisms responsible for lowering intraocular pressure (IOP) are not completely clear. The protein profile changes in primary human trabecular meshwork (TM) cells after two days treatment with a ROCK inhibitor were studied using label-free SWATH acquisition. These results provided significant data of key protein candidates underlying the effect of ROCK inhibitor. Using the sensitive label-free mass spectrometry approach with data-independent acquisition (SWATH-MS), we established a comprehensive TM proteome library. All raw data generated from IDA and SWATH acquisitions were uploaded and published in the Peptide Atlas public repository (http://www.peptideatlas.org/) for general release (Data ID PASS01254).

Oral consumption of Garcinia kola(Bitter kola) lowers intraocular pressure.

Garcinia kola (bitter kola) is locally ingested across the West African subregion. It has ocular hypotensive effects similar to some commonly used glaucoma medications when administered topically. The study assessed the effect of oral ingestion of G.kola on intraocular pressure (IOP). A randomized, single-blind, placebo-controlled, cross-over design was used in this study. Forty-six healthy subjects, aged between 19 and 27years were recruited and randomized into two groups (A and B). Subjects in group A ingested 100mg/kg body weight bitter kola in a 200ml solution on their first visit and group B ingested 200ml of water. On the second visit, the order of treatment was reversed, IOP was measured at baseline and every 45min interval for 135min. The mean difference between the baseline and post-treatment IOP measurements were tested for statistical significance using repeated-measures analysis of variance (95% confidence intervals [CIs]). Mean IOP measurements decreased by 7.9, 18.2 and 20.6% at 45, 90 and 135min, respectively, after G.kola treatment. The reduction, though variable across subjects, was statistically significant (F [2.13, 95.62]=90.35, p<0.0001) across the respective time points. Repetition of an identical protocol without G. kola caused clinically negligible changes in IOP. There was no statistically significant influence of gender or age in G.kola effect on IOP reading. Oral ingestion of G.kola lowered the intraocular pressure of healthy young adults by 21%. Such an effect may be of therapeutic benefit to patients with POAG or ocular hypertension in low-income settings.

Brimonidine-LAPONITE® intravitreal formulation has an ocular hypotensive and neuroprotective effect throughout 6 months of follow-up in a glaucoma animal model.

Intravitreal administration is widely used in ophthalmological practice to maintain therapeutic drug levels near the neuroretina and because drug delivery systems are necessary to avoid reinjections and sight-threatening side effects. However, currently there is no intravitreal treatment for glaucoma. The brimonidine-LAPONITE® formulation was created with the aim of treating glaucoma for extended periods with a single intravitreal injection. Glaucoma was induced by producing ocular hypertension in two rat cohorts: [BRI-LAP] and [non-bri], with and without treatment, respectively. Eyes treated with brimonidine-LAPONITE® showed lower ocular pressure levels up to week 8 (p < 0.001), functional neuroprotection explored by scotopic and photopic negative response electroretinography (p = 0.042), and structural protection of the retina, retinal nerve fibre layer and ganglion cell layer (p = 0.038), especially on the superior-inferior axis explored by optical coherence tomography, which was corroborated by a higher retinal ganglion cell count (p = 0.040) using immunohistochemistry (Brn3a antibody) up to the end of the study (week 24). Furthermore, delayed neuroprotection was detected in the contralateral eye. Brimonidine was detected in treated rat eyes for up to 6 months. Brimonidine-LAPONITE® seems to be a potential sustained-delivery intravitreal drug for glaucoma treatment.

Intraocular pressure reduction with once-a-day application of a new prostaglandin eye drop: a pilot placebo-controlled study in 12 patients.

To assess the ocular hypotensive effect of 15-keto fluprostenol, the oxidized metabolite of travoprost, on glaucoma patients, through a randomized double-masked placebo-controlled study. Twelve patients with ocular normal tension glaucoma (NTG) (intraocular pressure [IOP] < 22mmHg) were enrolled. In order to ensure patient compliance to treatment, all study subjects were hospitalized. In each patient, the eye to be submitted to the treatments was randomly chosen. After hospital admission (day 1), those patients received for 5days at 8P.M. either one drop of 15-keto fluprostenol (35μg/ml) or one drop of placebo. IOP evaluation was performed within 8A.M. and 8P.M. for 6days. Furthermore, we performed a determination of cardiovascular parameters before and after the treatments. Starting with the first IOP measurement after the first treatment (8A.M. on day 2), IOP was reduced of about 14% in the eyes treated 15-keto fluprostenol, in comparison with baseline IOP values of 15-keto fluprostenol-treated patients. The IOP reduction in the 15-keto fluprostenol-treated group was significantly compared to placebo group (p < 0.05) starting from day 3 till day 6 of the study. Except for mild hyperemia in one 15-keto fluprostenol-treated eye, no other side effects were observed or reported by the enrolled patients. The travoprost metabolite 15-keto fluprostenol was effective in decrease IOP and maintained IOP reduction along 5days of treatment. The 15-keto fluprostenol can be developed as a good candidate for once-a-day NTG patients' treatment.