June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Protective Effects of Adenoviral Mediated Subconjunctival Delivery of BMP2 in an Experimental Glaucoma Model
Author Affiliations & Notes
  • Pedro Gonzalez
    Ophthalmology, Duke Eye Center, Duke University, Durham, NC
  • Coralia Catalina Luna
    Ophthalmology, Duke Eye Center, Duke University, Durham, NC
  • Ian Campbell
    Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
    Rehabilitation Research and Development Center of Excellence, VA Medical Center, Atlanta, GA
  • C Ross Ethier
    Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA
    Rehabilitation Research and Development Center of Excellence, VA Medical Center, Atlanta, GA
  • Footnotes
    Commercial Relationships Pedro Gonzalez, None; Coralia Luna, None; Ian Campbell, None; C Ethier, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2006. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

To investigate the therapeutic potential of BMP2 delivery to the sclera to prevent axon loss in an experimental model of glaucoma.

 
Methods
 

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).

 
Results
 

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.

 
Conclusions
 

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.  

 
Figure 1. Protective effects of adenoviral mediated subconjunctival delivery of BMP2 in an experimental glaucoma. Left: IOP was elevated by carbomer in both Ad.CMV.BMP2 and AD.CMV.EGFP treated eyes. IOP burden= IOP times duration. “Ctrl” are naïve animals with no IOP elevation. * p<0.0001. Middle: Eyes treated with BMP2 had more RGC axons than controls treated with GFP after IOP elevation. Right: Axon loss relative to controls. Number of eyes: Control n=8; BMP2=14; GFP=13. ** p<0.003. Bars are SD.
 
Figure 1. Protective effects of adenoviral mediated subconjunctival delivery of BMP2 in an experimental glaucoma. Left: IOP was elevated by carbomer in both Ad.CMV.BMP2 and AD.CMV.EGFP treated eyes. IOP burden= IOP times duration. “Ctrl” are naïve animals with no IOP elevation. * p<0.0001. Middle: Eyes treated with BMP2 had more RGC axons than controls treated with GFP after IOP elevation. Right: Axon loss relative to controls. Number of eyes: Control n=8; BMP2=14; GFP=13. ** p<0.003. Bars are SD.

 
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