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Abstract #19654 Published in IGR 9-3
Targeting amyloid-β in glaucoma treatment
Guo L; Salt TE; Luong V; Wood N; Cheung W; Maass A; Ferrari G; Russo-Marie F; Sillito AM; Cheetham MEProceedings of the National Academy of Sciences of the United States of America 2007; 104: 13444-13449
See also comment(s) by Robert N. Weinreb • Jonathan Crowston & Yeni Yucel & Balwantray Chauhan & Keith Martin & Art Neufeld & Lan Wang & Chris Leung & James Morgan & Ian Trounce • Francesca Cordeiro & Li Guo •
The development of the devastating neurodegenerative condition, Alzheimer's disease, is strongly associated with amyloid-β (Aβ) deposition, neuronal apoptosis, and cell loss. Here, we provide evidence that implicates these same mechanisms in the retinal disease glaucoma, a major cause of irreversible blindness worldwide, previously associated simply with the effects of intraocular pressure. We show that Aβ colocalizes with apoptotic retinal ganglion cells (RGC) in experimental glaucoma and induces significant RGC apoptosis in vivo in a dose- and time-dependent manner. We demonstrate that targeting different components of the Aβ formation and aggregation pathway can effectively reduce glaucomatous RGC apoptosis in vivo, and finally, that combining treatments (triple therapy) is more effective than monotherapy. Our work suggests that targeting the Aβ pathway provides a therapeutic avenue in glaucoma management. Furthermore, our work demonstrates that the combination of agents affecting multiple stages in the Aβ pathway may be the most effective strategy in Aβ-related diseases.
Dr. M.F. Cordeiro, Glaucoma and Retinal Degeneration, Research Group, Pathology, University College London Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK. M.cordeiro@ucl.ac.uk
Classification:
1.3 Pathogenesis (Part of: 1 General aspects)
11.8 Neuroprotection (Part of: 11 Medical treatment)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
3.3 Immunohistochemistry (Part of: 3 Laboratory methods)
