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Guorong Li, Pedro Gonzalez, Sina Farsiu, W Daniel Stamer; Dynamic alterations in conventional outflow function in Bmp2-induced ocular hypertensive mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2915.
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The goal of this study was to evaluate changes in outflow facility and morphology of the outflow pathway by Spectral Domain Optical Coherence Tomography (SD-OCT) in mice after induction of glaucoma by delivery and overexpression of Bmp2 (bone morphogenetic protein 2) gene to conventional outflow cells.
An adenovirus expressing Bmp2 gene driven by CMV promoter was delivered intracamerally to mice. Intraocular pressure (IOP) was measured pre- and post-infusion twice a week for 36d by rebound tonometery. Outflow facility and IOP was measured by direct cannulation of anterior chamber at 7d, 14d and 36d after viral infusion in living mice. Morphology of outflow tract was followed by SD-OCT and standard histology. Retinal ganglion cell (RGC) health was evaluated by Brn3a labeling of retina flat mounts and axon counts of optic nerves.
Overexpression of Bmp2 significantly increased IOP in a biphasic manner; reaching a maximum of ~40 mmHg at day 10, recovering to ~25 mmHg on day 20 and elevating to ~30 mmHg until day 36. IOP in the contralateral control eyes measured ~13 mmHg at all time points. Outflow facility decreased significantly at 7d (0.0049 ± 0.0018 μl/min/mmHg vs 0.0024 ± 0.0012, p=0.034, n=4), 14d (0.0041 ± 0.00096 vs 0.0014 ± 0.00048, p=0.0495, n=3) and 36d (0.0032 ± 0.0019 vs 0.0018 ± 0.0017, p=0.038, n=4). OCT analyses of Bmp-2 expressing eyes showed increased thickness of the cornea (95 ± 4.24 μm vs 119.5 ± 26.16, n=2) and trabecular meshwork (TM) (16 ± 2.83 μm vs 22 ± 0, n=2). Histological data confirmed the OCT findings. OCT also showed that Schelmm’s canal (SC) was less responsive to IOP pressure steps (IOP from 10 to 15 mmHg, SC area reduced 31% in control and 10.4% in Bmp2 eyes, n=2) at 10d. There were significantly fewer RGC bodies in peripheral retinal and fewer axons in optic nerve Bmp2 expressing eyes at 36d.
The increase in IOP induced by Bmp2 gene delivery to the mouse anterior chamber may result from the accumulation of ECM in outflow pathway, leading to increased stiffness of TM and compromised homeostatic responsiveness to IOP. Further investigations are needed to determine the mechanism of Bmp2-induced increase in outflow resistance, and value of Bmp2 overexpression as a mouse glaucoma model.
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