title: Disease progression in iridocorneal angle tissues of BMP2-induced ocular hypertensive mice with optical coherence tomography.
abstract: OBJECTIVE
  The goal of the present study was to test for the first time whether glaucomatous-like disease progression in a mouse can be assessed morphologically and functionally with spectral domain optical coherence tomography (SD-OCT).
  
  
  METHODS
  We monitored progressive changes in conventional outflow tissues of living mice overexpressing human bone morphogenetic protein 2 (BMP2), a model for glaucoma. Intraocular pressure (IOP) and outflow tissue morphology/Young's modulus were followed in mice for 36 days with rebound tonometry and SD-OCT, respectively. Results were compared to standard histological methods. Outflow facility was calculated from flow measurements with direct cannulation of anterior chambers subjected to three sequential pressure steps.
  
  
  RESULTS
  Overexpression of BMP2 significantly elevated IOP in a biphasic manner over time compared to mice that overexpressed green fluorescent protein in outflow cells and naïve controls. SD-OCT revealed changes in outflow tissues overexpressing BMP2 that corresponded with the timing of the IOP phases and decreased outflow facility. In the first phase, the angle was open, but the trabecular meshwork and the cornea were thickened. OCT detected increased trabecular meshwork stiffness after provocative IOP challenges of the BMP2 eyes, which corresponded to increased collagen deposition with transmission electron microscopy. In contrast, the angle was closed in the second phase. IOP elevation over 36 days due to BMP2 overexpression resulted in significant retinal ganglion cell and axon loss.
  
  
  CONCLUSIONS
  Although not a feasible open-angle glaucoma model, the BMP2 mice were useful for demonstrating the utility of SD-OCT in following disease progression and differentiating between two forms of ocular pathology over time that resulted in ocular hypertension.
authors.affiliation: Department of Ophthalmology, Duke University, Durham, NC.
authors.forename: Guorong
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Duke University, Durham, NC ; Department of Biomedical Engineering, Duke University, Durham, NC.
authors.forename: Sina
authors.initials: S
authors.lastname: Farsiu
authors.affiliation: Department of Ophthalmology, Duke University, Durham, NC.
authors.forename: Jianming
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Ophthalmology, Duke University, Durham, NC.
authors.forename: Angela
authors.initials: A
authors.lastname: Dixon
authors.affiliation: School of Astronautics, Harbin Institute of Technology, Harbin, China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Ophthalmology, Duke University, Durham, NC ; Department of Neurobiology, Duke University, Durham, NC.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: McKinnon
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC.
authors.forename: Fan
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Ophthalmology, Duke University, Durham, NC.
authors.forename: Pedro
authors.initials: P
authors.lastname: Gonzalez
authors.affiliation: Department of Ophthalmology, Duke University, Durham, NC ; Department of Biomedical Engineering, Duke University, Durham, NC.
authors.forename: W Daniel
authors.initials: WD
authors.lastname: Stamer
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000473:pathology / Q000503:physiopathology; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism*; D003315:Cornea / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005902:Glaucoma, Open-Angle / Q000209:etiology; D006801:Humans; D007429:Intraocular Pressure; D007498:Iris / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009798:Ocular Hypertension / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D041623:Tomography, Optical Coherence / Q000379:methods
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins