title: Microbead-induced ocular hypertensive mouse model for screening and testing of aqueous production suppressants for glaucoma.
abstract: OBJECTIVE
  To characterize the microbead-induced ocular hypertension (OHT) mouse model and investigate its potential use for preclinical screening and evaluation of ocular hypotensive agents, we tested the model's responses to major antiglaucoma drugs.
  
  
  METHODS
  Adult C57BL/6J mice were induced to develop OHT unilaterally by intracameral injection of microbeads. The effects of the most commonly used ocular hypotensive drugs, including timolol, brimonidine, brinzolamide, pilocarpine, and latanoprost, on IOP and glaucomatous neural damage were evaluated. Degeneration of retinal ganglion cells (RGCs) and optic nerve axons were quantitatively assessed using immunofluorescence labeling and histochemistry. Thickness of the ganglion cell complex (GCC) was also assessed with spectral-domain optical coherence tomography (SD-OCT).
  
  
  RESULTS
  A microbead-induced OHT model promptly responded to drugs, such as timolol, brimonidine, and brinzolamide, that lower IOP through suppressing aqueous humor production and showed improved RGC and axon survival as compared to vehicle controls. Accordingly, SD-OCT detected significantly less reduction of GCC thickness in mice treated with all three aqueous production suppressants as compared to the vehicle contol-treated group. In contrast, drugs that increase aqueous outflow, such as pilocarpine and latanoprost, failed to decrease IOP in the microbead-induced OHT mice.
  
  
  CONCLUSIONS
  Microbead-induced OHT mice carry dysfunctional aqueous outflow facility and therefore offer a unique model that allows selective screening of aqueous production suppressant antiglaucoma drugs or for studying the mechanisms regulating aqueous humor production. Our data set the stage for using GCC thickness assessed by SD-OCT as an imaging biomarker for noninvasive tracking of neuronal benefits of glaucoma therapy in this model.
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, P. R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yang
authors.forename: Kin-Sang
authors.initials: KS
authors.lastname: Cho
authors.forename: Huihui
authors.initials: H
authors.lastname: Chen
authors.forename: Dekuang
authors.initials: D
authors.lastname: Yu
authors.forename: Wan-Heng
authors.initials: WH
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Luo
authors.forename: Iok-Hou
authors.initials: IH
authors.lastname: Pang
authors.forename: Wenyi
authors.initials: W
authors.lastname: Guo
authors.forename: Dong Feng
authors.initials: DF
authors.lastname: Chen
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000187:drug effects; D000068438:Brimonidine Tartrate; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005240:Feasibility Studies; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D018721:Muscarinic Agonists / Q000627:therapeutic use*; D009798:Ocular Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D009900:Optic Nerve / Q000187:drug effects* / Q000503:physiopathology; D010862:Pilocarpine / Q000627:therapeutic use; D011461:Prostaglandins F, Synthetic / Q000627:therapeutic use; D011810:Quinoxalines / Q000627:therapeutic use; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use; D013843:Thiazines / Q000627:therapeutic use; D013999:Timolol / Q000627:therapeutic use; D041623:Tomography, Optical Coherence
chemical_list: D000959:Antihypertensive Agents; D002257:Carbonic Anhydrase Inhibitors; D018721:Muscarinic Agonists; D011461:Prostaglandins F, Synthetic; D011810:Quinoxalines; D013449:Sulfonamides; D013843:Thiazines; D010862:Pilocarpine; D000068438:Brimonidine Tartrate; D000077338:Latanoprost; D013999:Timolol; C111827:brinzolamide