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L. Guo, T. E. Salt, V. Luong, G. Ferrarl, W. Cheung, N. Wood, F. Russo-Marie, M. E. Cheetham, S. E. Moss, M. F. Cordeiro; Targeting Alzheimer Protein Beta Amyloid for Treatment in Glaucoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4370.
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We have previously demonstrated that the Alzheimer protein Beta Amyloid (Aß) is strongly implicated in the development of retinal ganglion cell (RGC) apoptosis in glaucoma. In this study, we have investigated the effects of different approaches to targeting Aß in experimental glaucoma.
A rat model of chronic ocular hypertension (OHT) was made as previously described. Animals were treated at the time of surgical IOP elevation (0 weeks), with the following treatments targeting Aß (all 5 µl intravitreal injections): Aß antibody (0.5mg/ml, n=5), Congo red (1.46mg/ml, n=5), ß-secretase inhibitor II (10ug/ml, n=5), and IgG1k purified protein (null antibody, 0.5mg/ml, n=5) as control. All treated animals were imaged in vivo with our recently established DARC (Detection of Apoptosing Retinal Cells) imaging method at baseline, 3, 8 and 16 weeks and then sacrificed for histology.
All treatments targeting Aß showed reduced RGC apoptosis compared to control OHT at 3 weeks. Aß antibody resulted in a significant reduction of RGC apoptosis at 3 (p<0.05) and 8 (p<0.01) weeks after IOP elevation. Congo red showed significant reduction of RGC apoptosis at 3 (p<0.05) but not 8 and 16 weeks. ß-secretase inhibitor showed a modest reduction of RGC apoptosis at 3 weeks but this did not reach significance compared to control, with no significant effects at 8 and 16 weeks following IOP elevation.
Our results strongly suggest Aß to be involved in the development of experimental glaucoma. We demonstrate for the first time that targeting Aß formation and aggregation may be a potential approach in the treatment of glaucoma. Furthermore, a single injection of the Aß antibody produced prolonged and significant effects. We believe that the Aß antibody represents an exciting and novel therapeutic strategy in glaucomatous disease.
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