advertisement

---

1 General aspects (0)   1.1 Epidemiology (11)   1.2 Population genetics (0)   1.3 Pathogenesis (4)   1.4 Quality of life (12)   1.5 Glaucomas as cause of blindness (5)   1.6 Prevention and screening (9) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (4)   2.2 Cornea (18)   2.3 Sclera (4)   2.4 Anterior chamber angle (4)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (7)     2.5.2 Schlemms canal (1)     2.5.3 Scleral outlet channels (0)   2.6 Aqueous humor dynamics (1)     2.6.1 Production (0)     2.6.2 Outflow (2)       2.6.2.1 Trabecular meshwork (1)       2.6.2.2 Uveoscleral (0)     2.6.3 Compostion (1)   2.7 Episcleral veins and venous pressure (1)   2.8 Iris (2)   2.9 Ciliary body (1)   2.10 Lens (0)   2.11 Vitreous body (1)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (1)   2.13 Retina and retinal nerve fibre layer (16)   2.14 Optic disc (8)   2.15 Optic nerve (1)   2.16 Chiasma and retrochiasmal central nervous system (9)   2.17 Stem cells (1)   2.20 Other (0) 3 Laboratory methods (0)   3.1 Microscopy (2)   3.2 Electron microscopy (4)   3.3 Immunohistochemistry (5)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (0)     3.4.2 Gene studies (33)   3.5 Molecular biology incl. SiRNA (16)   3.6 Cellular biology (22)   3.7 Biochemistry (5)   3.8 Pharmacology (5)   3.9 Pathophysiology (10)   3.10 Immunobiology (2)   3.11 Pharmacogenetics (0)   3.12 Proteomics (1)   3.13 In vivo imaging (0)     3.13.1 Laser Scanning (0)       3.13.1.1 Confocal Scanning Laser Ophthalmoscopy (0)       3.13.1.2 Confocal Scanning Laser Polarimetry (0)     3.13.2 Optical Coherence Tomography (0)       3.13.2.1 Anterior Segment (0)       3.13.2.2 Posterior Segment (0)     3.13.3 RGC Imaging (0)     3.13.4 Other (0)   3.20 Other (0) 4 Tissue culture of ocular cells (0) 5 Experimental glaucoma; animal models (1)   5.1 Rodent (24)   5.2 Primates (7)   5.3 Other (21) 6 Clinical examination methods (0)   6.1 Intraocular pressure measurement; factors affecting IOP (0)     6.1.1 Devices, techniques (9)     6.1.2 Fluctuation, circadian rhythms (6)     6.1.3 Factors affecting IOP (13)   6.2 Tonography, aqueous flow measurement (see also 2.6) (1)   6.3 Biomicroscopy (slitlamp) (0)     6.3.1 Anterior segment (0)     6.3.2 Posterior segment (0)   6.4 Gonioscopy (2)   6.5 Ophthalmoscopy (0)   6.6 Visual field examination and other visual function tests (0)     6.6.1 Conventional manual (5)     6.6.2 Automated (12)     6.6.3 Special methods (e.g. color, contrast, SWAP etc.) (10)   6.7 Electro-ophthalmodiagnosis (7)   6.8 Photography (0)     6.8.1 Anterior segment (6)     6.8.2 Posterior segment (7)   6.9 Computerized image analysis (0)     6.9.1 Laser scanning (0)       6.9.1.1 Confocal Scanning Laser Ophthalmoscopy (20)       6.9.1.2 Confocal Scanning Laser Polarimetry (12)     6.9.2 Optical coherence tomography (0)       6.9.2.1 Anterior (6)       6.9.2.2 Posterior (29)     6.9.5 Other (0)   6.10 Fluorescein (ICG) angiography (0)     6.10.1 Anterior segment (1)     6.10.2 Posterior segment (0)   6.11 Bloodflow measurements (23)   6.12 Ultrasonography and ultrasound biomicroscopy (7)   6.13 Provocative tests (2)   6.19 Telemedicine (0)   6.20 Progression (4)   6.30 Other (8) 8 Refractive errors in relation to glaucoma (0)   8.1 Myopia (1)   8.2 Hypermetropia (0)   8.3 Contact lenses (0)   8.4 Refractive surgical procedures (1)   8.5 Other (0) 9 Clinical forms of glaucomas (0)   9.1 Developmental glaucomas (1)     9.1.1 Congenital glaucoma, Buphthalmos (4)     9.1.2 Juvenile glaucoma (7)     9.1.3 Syndromes of Axenfeld, Rieger, Peters, aniridia (3)     9.1.4 Other (0)   9.2 Primary open angle glaucomas (0)     9.2.1 Ocular hypertension (3)     9.2.2 Other risk factors for glaucoma (1)     9.2.3 Open angle glaucoma with elevated IOP (2)     9.2.4 Normal pressure glaucoma (17)   9.3 Primary angle closure glaucomas (0)     9.3.1 Acute primary angle closure glaucoma (pupillary block) (12)     9.3.2 Chronic primary angle closure glaucoma (pupillary block) (3)     9.3.3 Plateau iris syndrome (0)     9.3.4 Primary angle closure suspect (2)     9.3.5 Primary angle closure (0)     9.3.10 Other (0)   9.4 Glaucomas associated with other ocular and systemic disorders (0)     9.4.1 Steroid-induced glaucoma (8)     9.4.2 Glaucomas associated with disorders of the cornea, conjunctiva, sclera (1)       9.4.2.1 Iridocorneal endothelial syndrome (ICE, incl. irisatrophy) (0)       9.4.2.2 Posterior polymorphous dystrophy (0)       9.4.2.3 Fuchs' endothelial dystrophy (1)       9.4.2.5 Other (0)     9.4.3 Glaucomas associated with disorders of the iris and ciliary body (0)       9.4.3.1 Pigmentary glaucoma (3)       9.4.3.5 Other (3)     9.4.4 Glaucomas associated with disorders of the lens (0)       9.4.4.1 Exfoliation syndrome (10)       9.4.4.2 Glaucomas associated with cataracts (0)       9.4.4.3 Glaucomas associated with lens dislocation (2)       9.4.4.5 Other (2)     9.4.5 Glaucomas associated with disorders of the retina, choroid and vitreous (0)       9.4.5.1 Neovascular glaucoma (16)       9.4.5.5 Other (7)     9.4.6 Glaucomas associated with inflammation, uveitis (4)     9.4.7 Glaucomas associated with ocular trauma (5)     9.4.8 Glaucomas associated with intraocular tumors (0)     9.4.9 Glaucomas associated with elevated episcleral venous pressure (0)       9.4.10 Glaucomas associated with hemorrhage (2)     9.4.11 Glaucomas following intraocular surgery (0)       9.4.11.1 Ciliary block (malignant) glaucoma (1)       9.4.11.2 Glaucomas in aphakia and pseudophakia (4)       9.4.11.3 Epithelial, fibrous, and endothelial proliferation (0)       9.4.11.4 Glaucomas associated with corneal surgery (6)       9.4.11.5 Glaucomas associated with vitreoretinal surgery (7)     9.4.15 Glaucoma in relation to systemic disease (26)     9.4.20 Other (1) 10 Differential diagnosis e.g. anterior and posterior ischemic optic neuropathy (2) 11 Medical treatment (0)   11.1 General management, indication (4)   11.2 Cholinergic drugs (0)   11.3 Adrenergic drugs (0)     11.3.1 Epinephrine (0)     11.3.2 Thymoxamine, dapiprazole (0)     11.3.3 Apraclonidine, brimonidine (1)     11.3.4 Betablocker (13)     11.3.5 Other (0)   11.4 Prostaglandins (40)   11.5 Carbonic anhydrase inhibitors (0)     11.5.1 Systemic (2)     11.5.2 Topical (7)   11.6 Osmotic treatment (0)   11.7 Treatment of bloodflow (0)   11.8 Neuroprotection (30)   11.9 Gene therapy (3)   11.13 Combination therapy (0)     11.13.1 Betablocker and pilocarpine (0)     11.13.2 Betablocker and carbon anhydrase inhibitor (2)     11.13.3 Betablocker and brimonidine (2)     11.13.4 Betablocker and prostaglandin (7)     11.13.5 Other (0)   11.14 Investigational drugs; pharmacological experiments (37)   11.15 Other drugs in relation to glaucoma (19)   11.16 Vehicles, delivery systems, pharmacokinetics, formulation (10)   11.17 Cooperation with medical therapy e.g. persistency, compliance, adherence (7)   11.20 Other (0) 12 Surgical treatment (0)   12.1 General management, indication (1)   12.2 Laser iridotomy (5)   12.3 Laser iridoplasty (0)   12.4 Laser trabeculoplasty and other laser treatment of the angle (8)   12.7 Surgical iridectomy (0)   12.8 Filtering surgery (0)     12.8.1 Without tube implant (18)     12.8.2 With tube implant or other drainage devices (23)     12.8.3 Non-perforating (5)     12.8.4 Using laser (0)     12.8.5 Other (0)     12.8.10 Woundhealing antifibrosis (14)     12.8.11 Complications, endophthalmitis (9)   12.9 Trabeculotomy, goniotomy (1)   12.10 Cyclodestruction (5)   12.11 Cyclodialysis (0)   12.12 Cataract extraction (0)     12.12.1 Intracapsular (0)     12.12.2 Extracapsular (0)     12.12.3 Phacoemulsification (7)   12.14 Combined cataract extraction and glaucoma surgery (0)     12.14.1 Intracapsular (0)     12.14.2 Extracapsular (0)     12.14.3 Phacoemulsification (15)   12.15 Capsulotomy (0)   12.16 Vitrectomy (0)   12.17 Anesthesia (3)   12.20 Other (9) 13 Therapeutic prognosis and outcome (0)   13.1 Prognostic factors (0)   13.2 Outcome (0)     13.2.1 IOP (1)     13.2.2 Visual field (0)       13.2.2.1 Progression (2)       13.2.2.2 Improvement (0)     13.2.3 Other (0) 14 Costing studies; pharmacoeconomics (7) 15 Miscellaneous (8)

---

Abstract #25187 Published in IGR 12-1

Reduced myocilin expression in cultured monkey trabecular meshwork cells induced by a selective glucocorticoid receptor agonist: comparison with steroids

Pfeffer BA; DeWitt CA; Salvador-Silva M; Cavet ME; López FJ; Ward KW
Investigative Ophthalmology and Visual Science 2010; 51: 437-446

---

PURPOSE: To assess in vitro myocilin (MYOC) expression in trabecular meshwork (TM) cells exposed to BOL-303242-X, a selective glucocorticoid receptor (GR) agonist (SEGRA), in comparison with dexamethasone (DEX), and prednisolone acetate (PA). METHODS: After drug treatment of monkey TM cultures, MYOC protein in conditioned media (CM) was measured by Western blot and densitometry. MYOC mRNA levels were analyzed by qRT-PCR. RU-486 was tested for antagonism of MYOC protein expression induced by DEX and BOL-303242-X. RESULTS: Baseline MYOC protein released into CM and MYOC mRNA were detected. DEX or PA elicited dose-dependent increases in MYOC in CM and also in MYOC mRNA. BOL-303242-X effects typified partial agonism, with significantly reduced MYOC protein and mRNA, compared with DEX. Maximum efficacy for BOL-303242-X was 53% of that for DEX. Mean EC(50) across all strains tested was lower, but not significantly different, for BOL-303242-X versus DEX. Compared with DEX, MYOC mRNA levels were significantly lower in BOL-303242-X-treated TM cells at the highest doses tested. EC(50)s for PA were higher than DEX, for both myocilin protein and mRNA. RU-486 displayed a dose-dependent antagonism to drug-induced increases in myocilin levels. CONCLUSIONS: In vitro quantitative assays of myocilin expression in TM cells can be used for characterizing anti-inflammatory drugs that are GR ligands. The results suggest that, compared with traditional ocular steroids, therapeutic doses of BOL-303242-X elicit a reduced myocilin expression profile in TM cells by virtue of the partial agonist properties of this compound.

Preclinical Pharmacology Department, Pharmaceutical Research and Development, Bausch & Lomb, Inc, Rochester, New York 14609, USA. bruce_pfeffer@bausch.com

---

Classification:

5.2 Primates (Part of: 5 Experimental glaucoma; animal models)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
9.4.1 Steroid-induced glaucoma (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)

---

• ← Previous
• Next →

---