Abstract
Purpose: :
Angiogenesis plays an essential role in several diseases of the eye, but existing anti-angiogenic therapies have limited benefits. Here, we report the anti-angiogenic effects of a murine monoclonal antibody, CL1-R2, in the classical mouse model of pre-retinal neovascularization recapitulating many features of the retinopathy of prematurity.
Methods: :
The murine anti-CD160 CL1-R2 mAb was developed and evaluated as an anti CD160 mAb during the 7th human Leukocyte Differentiation Antigen workshop. We used C57BL/8J seven days pups for the ischemic retinopathy experiments. 1 microliter -0 microliter for the control animals- of CL1-R2 mAb or Bevacizumab or IgG1 isotype control was injected into the vitreous cavity of each eye at post natal 12. There were at least 12 mouse examined for each treatment. Mice were killed at P17. some mice underwent retinal Ex vivo angiography and histological examinations were performed for each eye. Countings of the retinal neovessels including that of neobuclei and of neovascular lumens diameters were performed as well immunohistochemistry experiments targeting normal vascular cells and abnormal neovascular cells.
Results: :
The outcome of the ensemble of experiments is unequivocal and demonstrates a dramatic antiangiogenic effect of the CL1-R2 antibody with a normalization of treated neovessels.It must be emphasized that the concentrations used with with the CL1-R2 antibody were much lower than those used for Bevacizumab.
Conclusions: :
The dramatic therapeutic effect of this antibody on this animal models of retinal neovascularization, acting according a complete different mechanism as compared to those of the available antiangiogenic drugs commercialized so far, offers a strong hope of the development of a very potent and enduring treatment for retinal neovascular diseases including diabetic retinopathy and choroidal neovascular Age related macular degeneration. It would not be surprising if this novel antibody becomes a revolutionary therapy for many malignancies including retiniblastoma.
Keywords: diabetic retinopathy • retinopathy of prematurity • neovascularization