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https://www.readbyqxmd.com/read/28632458/aquaporins-novel-targets-for-age-related-ocular-disorders
#1
Rajkumar Patil, Haishan Wang, Najam A Sharif, Alok Mitra
Aquaporins (AQPs), a large family of membrane protein channels that facilitate transport of water and other small solutes, play important roles in physiological functions and human diseases. Up till now, 13 types of AQPs, numbered 0 through 12, have been identified in various mammalian tissues. Homologous genes for AQPs in amphibians, insects, and bacteria highlight the evolutionary conservation and, thus, the importance of these membrane channels. Many members of the AQP family are expressed in the eye. AQP1, which is a water-selective channel, is expressed in the anterior chamber (cornea, ciliary body, trabecular meshwork) and posterior chamber (retina and microvessels in choroid), controlling the fluid homeostasis in the eye...
June 20, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28621684/expression-of-hypothalamic-neurohormones-and-their-receptors-in-the-human-eye
#2
Sander R Dubovy, Maria P Fernandez, Jose J Echegaray, Norman L Block, Noriyuki Unoki, Roberto Perez, Irving Vidaurre, Richard K Lee, Mehrdad Nadji, Andrew V Schally
Extrapituitary roles for hypothalamic neurohormones have recently become apparent and clinically relevant, based on the use of synthetic peptide analogs for the treatment of multiple conditions including cancers, pulmonary edema and myocardial infarction. In the eye, it has been suggested that some of these hormones and their receptors may be present in the ciliary body, iris, trabecular meshwork and retina, but their physiological role has yet to be elucidated. Our study intends to comprehensively demonstrate the expression of some hypothalamic neuroendocrine hormones and their receptors within different retinal and extraretinal structures of the human eye...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609185/discovery-and-preclinical-development-of-netarsudil-a-novel-ocular-hypotensive-agent-for-the-treatment-of-glaucoma
#3
Cheng-Wen Lin, Bryan Sherman, Lori A Moore, Carmen L Laethem, Da-Wen Lu, Padmanabhan P Pattabiraman, Ponugoti Vasantha Rao, Mitchell A deLong, Casey C Kopczynski
PURPOSE: Rho-associated protein kinase (ROCK) inhibitors lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM). The preclinical characterization of netarsudil, a new ROCK/norepinephrine transporter (NET) inhibitor currently in clinical development, is presented herein. METHODS: The kinase inhibitory activity of netarsudil was compared to its esterase metabolite, netarsudil-M1, and 3 other ROCK inhibitors using a commercially available kinase assay kit...
June 13, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28594895/atp-sensitive-potassium-katp-channel-openers-diazoxide-and-nicorandil-lower-intraocular-pressure-by-activating-the-erk1-2-signaling-pathway
#4
Uttio Roy Chowdhury, Cindy K Bahler, Bradley H Holman, Michael P Fautsch
Elevated intraocular pressure is the most prevalent and only treatable risk factor for glaucoma, a degenerative disease of the optic nerve. While treatment options to slow disease progression are available, all current therapeutic and surgical treatments have unwanted side effects or limited efficacy, resulting in the need to identify new options. Previous reports from our laboratory have established a novel ocular hypotensive effect of ATP-sensitive potassium channel (KATP) openers including diazoxide (DZ) and nicorandil (NCD)...
2017: PloS One
https://www.readbyqxmd.com/read/28593245/a-gpr119-signaling-system-in-the-murine-eye-regulates-intraocular-pressure-in-a-sex-dependent-manner
#5
Sally Miller, Sherry Shu-Jung Hu, Emma Leishman, Dan Morgan, Jim Wager-Miller, Ken Mackie, Heather B Bradshaw, Alex Straiker
Purpose: GPR119 is a G protein-coupled receptor that may be the endogenous target for 2-oleoylglycerol (2-OG), a lipid related to the endocannabinoid family of neuromodulators. Interest in GPR119 has centered on its role in regulating insulin secretion; however, the role of GPR119 has not been examined in the eye. The purpose of this study was to explore a potential GPR119-based signaling system in the murine eye. Methods: We used a combination of RT-PCR, immunohistochemistry, lipid measurement, and IOP measurement in a normotensive mouse model, with GPR119 knockout mice as controls...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28586796/functional-activity-of-matrix-metalloproteinases-2-and-9-in-tears-of-patients-with-glaucoma
#6
Prity Sahay, Aparna Rao, Debananda Padhy, Sarada Sarangi, Gopinath Das, Mamatha M Reddy, Rahul Modak
Purpose: To evaluate the differential expression of tear matrix metalloproteinases (MMP) 2 and 9 in of patients with various forms of glaucoma. Methods: Tear samples were collected with a Schirmer's strip from 148 eyes of 113 patients (medically naïve patients with primary open-angle [POAG] or angle closure glaucoma [PACG] and those with pseudoexfoliation syndrome [PXF] or glaucoma [PXG]). These were compared to patients undergoing cataract surgery (controls) for this cross-sectional study...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28584936/a-review-of-nitric-oxide-for-the-treatment-of-glaucomatous-disease
#7
REVIEW
Joah Aliancy, W Daniel Stamer, Barbara Wirostko
Glaucoma is the leading cause of irreversible blindness worldwide, affecting 64.3 million people. An estimated 60.5 million people are affected by primary open angle glaucoma globally, and this will increase to 111.8 million by 2040. The definition of glaucoma has evolved greatly over time. Although multiple risk factors such as ischemia, inflammation, myopia, race, age and low ocular perfusion pressure may play a role, intraocular pressure (IOP) is still the main risk factor we can easily identify and modify...
June 5, 2017: Ophthalmology and Therapy
https://www.readbyqxmd.com/read/28575917/-surgical-options-in-glaucoma-management
#8
Thomas S Dietlein, André Rosentreter
During the last few years, there has been a considerable capacity of innovations in glaucoma surgery owing to new micro-stents increasing the aqueous outflow via transscleral routes, via the trabecular meshwork or the suprachoroidal space. These interventions can be easily performed in combination with small-incision cataract surgery. Even the well-known filtering procedures, trabeculectomy and drainage device surgery, formerly perceived as being outdated, re-achieve better reputation owing to refinements in surgical technique and improved surgical experience...
June 2, 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28564705/a-histologic-categorization-of-aqueous-outflow-routes-in-familial-open-angle-glaucoma-and-associations-with-mutations-in-the-myoc-gene-in-japanese-patients
#9
Teruhiko Hamanaka, Masae Kimura, Tetsuro Sakurai, Nobuo Ishida, Jun Yasuda, Masao Nagasaki, Naoki Nariai, Atsushi Endo, Kei Homma, Fumiki Katsuoka, Yoichi Matsubara, Masayuki Yamamoto, Nobuo Fuse
Purpose: This study evaluated specific relationships between pathogenic mechanisms and genetic polymorphisms in primary open-angle glaucoma (POAG). We analyzed the morphologies of trabeculectomy specimens obtained from patients with familial POAG. Methods: We used light microscopy and transmission electron microscopy to examine specimens obtained from 17 eyes of 14 patients with familial POAG. We also conducted exome analyses of two families and used targeted Sanger sequencing to analyze samples obtained from the remaining patients...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28564657/relationship-between-elevated-intraocular-pressure-and-divided-peripapillary-sector-retinal-nerve-fiber-layer-thickness-in-a-cynomolgus-monkey-laser-induced-ocular-hypertension-model
#10
Tetsuro Noguchi, Masamitsu Shimazawa, Koji Hamaguchi, Tomoaki Araki, Naoto Horai, Hideaki Hara
AIMS: We investigated the relationship between elevated intraocular pressure (IOP) and changes in global and peripapillary sector retinal nerve fiber layer (RNFL) thickness around the optic nerve head (ONH) in the laser-induced ocular hypertension monkey model. METHODS: To induce high IOP, green laser photocoagulation burns were applied around the trabecular meshwork of 1 eye from each of 12 cynomolgus monkeys. The animals had been acclimated to IOP measurement under conscious conditions for more than 2 months, and IOP was chronologically measured...
June 1, 2017: Ophthalmic Research
https://www.readbyqxmd.com/read/28560459/%C3%AF-1-receptor-stimulation-protects-against-pressure-induced-damage-through-insr-mapk-signaling-in-human-trabecular-meshwork-cells
#11
Bo Meng, Hongyi Li, Xian Sun, Wei Qu, Binbin Yang, Fang Cheng, Liping Shi, Huiping Yuan
The purpose of the present study was to investigate the protective effect of the σ-1 receptor (Sig-1R) agonist (+)‑pentazocin (PTZ) on pressure-induced apoptosis and death of human trabecular meshwork cells (hTMCs). The expression levels of Sig‑1R and insulin receptor (InsR) were examined in hTMCs. Cells were cultured under a pressure of 0, 20, 40, 60 and 80 mmHg for 48 h, and under 80 mmHg for 44 h, after which the cells were treated with (+)‑PTZ (20 µM), N-(2-(3,4-dichlorophenyl)ethyl)-N‑methyl-2‑(dimethylamino) ethylamine (BD‑1063; 20 µM) administered 30 min prior to (+)‑PTZ, or BD‑1063 (20 µM) and then exposed to 80 mmHg again until the 48 h time‑point...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28557836/histopathology-of-failed-descemet-membrane-endothelial-transfer
#12
Jack Parker, Robert M Verdijk, Thomas M Müller, Itay Lavy, Marieke Bruinsma, Kathryn Colby, Perry S Binder, Gerrit R J Melles
OBJECTIVES: To describe the postmortem histologic features after an unsuccessful Descemet membrane endothelial transfer (DMET) and assess any potential clinical implications. METHODS: Postmortem, an eye from a patient who previously underwent unsuccessful DMET for pseudophakic bullous keratopathy (PPBK) was harvested and processed for morphologic evaluation. RESULTS: Clinically and histologically, the host cornea showed evidence of diffuse stromal edema...
May 26, 2017: Eye & Contact Lens
https://www.readbyqxmd.com/read/28556530/characterizing-differences-between-mscs-and-tm-cells-towards-autologous-stem-cell-therapies-for-the-glaucomatous-trabecular-meshwork
#13
Eric J Snider, R Taylor Vannatta, Lisa Schildmeyer, W Daniel Stamer, C Ross Ethier
Glaucoma, a leading cause of blindness, is characterized by an increase in intraocular pressure (IOP), which is largely determined by resistance to aqueous humor outflow through the trabecular meshwork (TM). In glaucoma, the cellularity of the TM is decreased, and, as a result, stem cell therapies for the TM represent a potential therapeutic option for restoring TM function and treating glaucoma patients. We here focus on adipose derived mesenchymal stem cells (MSCs) as a potential autologous cell source for TM regenerative medicine applications and describe characterization techniques at the messenger (RT-qPCR), protein (western blotting, flow cytometry), and functional (contractility, phagocytosis) levels to distinguish MSCs from TM cells...
May 26, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28546930/implantation-of-trabecular-micro-bypass-stent-using-a-novel-landing-strip-technique
#14
Cindy X Zheng, Marlene R Moster, Priyanka Gogte, Yang Dai, Remy S Manzi, Michael Waisbourd
AIM: To describe a novel technique of creating a landing strip within the trabecular meshwork to guide trabecular micro-bypass stent (iStent) implantation in patients who underwent phacoemulsification. METHODS: Thirty-four eyes from 30 patients who underwent iStent implantation after phacoemulsification from May 2014 to February 2015 were included in our retrospective study. All iStents were implanted via the "landing strip" technique. A 25-gauge microvitreoretinal blade was used to bisect the trabecular meshwork to less than 1 clock-hour, effectively creating a landing strip...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28526237/small-molecule-inhibition-of-wnt-signaling-abrogates-dexamethasone-induced-phenotype-of-primary-human-trabecular-meshwork-cells
#15
Sarah D Ahadome, Chi Zhang, Elizabeth Tannous, James Shen, Jie J Zheng
Trabecular meshwork (TM) cells are the governing regulators of the TM structure. When the functionality of these cells is impaired, the structure of the TM is perturbed which often results in increased ocular hypertension. High intraocular pressure is the most significant risk factor for steroid-induced glaucoma. Dexamethasone (Dex)-induced phenotype of TM cells is widely utilized as a model system to gain insight into mechanisms underlying damaged TM in glaucoma. In this study, to assess the possible role of abnormal Wnt signaling in steroid-induced glaucoma, we analyzed the effects of small-molecule Wnt signaling modulators on Dex-induced expression extracellular matrix proteins of primary human TM cells...
August 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28514956/transcriptome-analysis-for-the-identification-of-cellular-markers-related-to-trabecular-meshwork-differentiation
#16
Padmapriya Sathiyanathan, Cheryl Y Tay, Lawrence W Stanton
BACKGROUND: Development of primary open-angle glaucoma (POAG) is associated with the malfunctioning trabecular meshwork (TM). Cell therapy offers great potential for the treatment of POAG, but requires the generation of functional TM cells in vitro to replace the lost/dysfunctional cells. TM differentiation in vitro from various stem cell types must be monitored by the expression of specific markers. However, no single definitive marker of the TM has been identified. RESULTS: To identify robust markers of TM differentiation, we performed global transcriptome profiling using high-density oligonucleotide microarray on ex vivo TM tissue and cultured TM progenitors...
May 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28512420/a-case-of-iris-melanocytoma-demonstrating-diffuse-melanocytic-proliferation-with-uncontrolled-intraocular-pressure
#17
Mami Kusunose, Yuji Sakino, Yoshihiro Noda, Tsutomu Daa, Toshiaki Kubota
We report a rare case with histologically proven melanocytoma of the iris that demonstrated diffuse melanocytic proliferation with uncontrolled secondary glaucoma and investigate the etiology of the intraocular pressure elevation. The patient was a 78-year-old man with a history of darkened iris of his left eye. The intraocular pressure was 39 mm Hg. A slit-lamp examination showed a diffuse darkened iris, and a gonioscopic examination revealed open angle with circumferential heavy pigmentation. There was no pigment dispersion of the anterior chamber and no pigment deposition of the cornea...
January 2017: Case Reports in Ophthalmology
https://www.readbyqxmd.com/read/28494163/expression-of-14-3-3-zeta-protein-in-dexamethasone-treated-mice-and-human-tm-1-cells
#18
Qian Liu, Yiming Ye, Xianchai Lin, Yangfan Yang, Kaili Wu, Minbin Yu
PURPOSE: 14-3-3 zeta protein plays a potential protective role in neurodegenerative disease. Given that glaucoma and neurodegenerative diseases share a similar pathogenesis, it is possible that 14-3-3 zeta may have a similar protective effect in the glaucomatous process. In the present study, we measured the expression of 14-3-3 zeta in vivo (mouse eyes) and in vitro in a transformed human trabecular meshwork (HTM) cell line, TM-1, and assessed the possible roles of this protein in dexamethasone (DEX)-treated eyes and HTM cells...
May 11, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28488311/left-ventricular-noncompaction-cardiomyopathy-in-a-patient-with-trisomy-13-a-report-and-review-of-the-literature
#19
Anri Hayashi, Tomohiro Kumada, Fumihito Nozaki, Ikuko Hiejima, Minoru Shibata, Takashi Kusunoki, Tatsuya Fujii
Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by prominent trabecular meshwork, and it is thought to result from arrest of the normal compaction process during embryogenesis. Patients with LVNC may be asymptomatic or have symptoms ranging from heart failure to stroke, life-threatening arrhythmias, or sudden death. The frequency of LVNC in children has increased with longer clinical courses. About 80% of patients with trisomy 13 have a congenital cardiac abnormality, but a clinical description of LVNC with trisomy 13 is lacking because of its poor prognosis and lack of awareness about LVNC...
May 9, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28486513/angle-stability-and-outflow-in-dual-blade-ab-interno-trabeculectomy-with-active-versus-passive-chamber-management
#20
Chao Wang, Yalong Dang, Susannah Waxman, Xiaobo Xia, Robert N Weinreb, Nils A Loewen
PURPOSE: To compare intraoperative angle stability and postoperative outflow of two ab interno trabeculectomy devices that excise the trabecular meshwork with or without active aspiration and irrigation. We hypothesized that anterior segment optical coherence tomography (AS-OCT) allows for a quantitative comparison of intraoperative angle stability in a microincisional glaucoma surgery (MIGS) pig eye training model. METHODS: Twelve freshly enucleated porcine eyes were measured with AS-OCT at baseline, at the beginning of the procedure and at its conclusion to determine the anterior chamber depth (ACD) and the nasal angle α in degrees...
2017: PloS One
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