PMID- 22599582
OWN - NLM
STAT- MEDLINE
DCOM- 20120910
LR  - 20220311
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 53
IP  - 7
DP  - 2012 Jun 20
TI  - Microbead-induced ocular hypertensive mouse model for screening and testing of 
      aqueous production suppressants for glaucoma.
PG  - 3733-41
LID - 10.1167/iovs.12-9814 [doi]
AB  - PURPOSE: 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.
FAU - Yang, Qiang
AU  - Yang Q
AD  - Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, P. 
      R. China.
FAU - Cho, Kin-Sang
AU  - Cho KS
FAU - Chen, Huihui
AU  - Chen H
FAU - Yu, Dekuang
AU  - Yu D
FAU - Wang, Wan-Heng
AU  - Wang WH
FAU - Luo, Gang
AU  - Luo G
FAU - Pang, Iok-Hou
AU  - Pang IH
FAU - Guo, Wenyi
AU  - Guo W
FAU - Chen, Dong Feng
AU  - Chen DF
LA  - eng
GR  - I01 RX000110/RX/RRD VA/United States
GR  - R01 EY017641/EY/NEI NIH HHS/United States
GR  - R01EY017641/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120620
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Carbonic Anhydrase Inhibitors)
RN  - 0 (Muscarinic Agonists)
RN  - 0 (Prostaglandins F, Synthetic)
RN  - 0 (Quinoxalines)
RN  - 0 (Sulfonamides)
RN  - 0 (Thiazines)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - 4S9CL2DY2H (Brimonidine Tartrate)
RN  - 6Z5B6HVF6O (Latanoprost)
RN  - 817W3C6175 (Timolol)
RN  - 9451Z89515 (brinzolamide)
SB  - IM
MH  - Animals
MH  - Antihypertensive Agents/*therapeutic use
MH  - Aqueous Humor/drug effects
MH  - Brimonidine Tartrate
MH  - Carbonic Anhydrase Inhibitors/*therapeutic use
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Feasibility Studies
MH  - Intraocular Pressure/drug effects
MH  - Latanoprost
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microspheres
MH  - Muscarinic Agonists/*therapeutic use
MH  - Ocular Hypertension/chemically induced/*drug therapy
MH  - Optic Nerve/*drug effects/physiopathology
MH  - Pilocarpine/therapeutic use
MH  - Prostaglandins F, Synthetic/therapeutic use
MH  - Quinoxalines/therapeutic use
MH  - Retinal Ganglion Cells/*drug effects/pathology
MH  - Sulfonamides/therapeutic use
MH  - Thiazines/therapeutic use
MH  - Timolol/therapeutic use
MH  - Tomography, Optical Coherence
PMC - PMC3390181
COIS- Disclosure: Q. Yang, None; K.-S. Cho, None; H. Chen, None; D. Yu, None; W.-H. 
      Wang, Alcon (E); G. Luo, None; I.-H. Pang, Alcon (E); W. Guo, None; D.F. Chen, 
      Alcon (F)
EDAT- 2012/05/19 06:00
MHDA- 2012/09/11 06:00
PMCR- 2012/12/01
CRDT- 2012/05/19 06:00
PHST- 2012/05/19 06:00 [entrez]
PHST- 2012/05/19 06:00 [pubmed]
PHST- 2012/09/11 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - iovs.12-9814 [pii]
AID - 10.1167/iovs.12-9814 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2012 Jun 20;53(7):3733-41. doi: 10.1167/iovs.12-9814.