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Pedro Gonzalez, Coralia Catalina Luna, Ian Campbell, C Ross Ethier; Protective Effects of Adenoviral Mediated Subconjunctival Delivery of BMP2 in an Experimental Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2006.
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To investigate the therapeutic potential of BMP2 delivery to the sclera to prevent axon loss in an experimental model of glaucoma.
7-week-old male Sprague-Dawley rats were injected with 10 µL (108 pfu) of adenoviral vectors expressing either BMP2 (Ad.CMV.BMP2) or GFP (Ad.CMV.EGFP) in the subconjunctival space of each quadrant of the eye. Three days after injections, ocular hypertension was induced by carbomer injection into the anterior chamber and IOP was monitored by TonoLab tonometer. Nine days after carbomer injection, rats were sacrificed for histologic quantification of glaucomatous damage (RGC axon loss). To evaluate whether the virus alone could alter the stiffness of the cornea (thus interfering with tonometry), 3 rats were treated with the Ad.CMV.BMP2 virus in one eye and Ad.CMV.EGFP control virus in the contralateral eye. Two weeks after treatment, the eyes were cannulated in situ, IOP was set to 4 different levels (10-40 mmHg) using a saline column, and IOP was measured (TonoLab tonometer).
The mean IOP elevation induced by carbomer over the duration of the study was 17.8 mmHg. The IOP burden (IOP times duration) in carbomer-injected eyes was unaffected by BMP2 treatment (fig 1 left). BMP2 treatment conferred significant (p<0.003) protection against RGC loss, with axon counts close to those seen in control animals without ocular hypertension (fig 1 center and right). BMP2 treatment did not result in a detectable change in tonometric accuracy for IOP measurement.
Our results suggest that delivery of BMP2 to the sclera can be effective in protecting RGC in glaucoma. Future studies are needed to evaluate longer duration effects and whether such effects result from increased rigidity of the sclera, direct neuroprotection of the retina, or both.
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