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Targeting amyloid-β in glaucoma treatment

Guo, Li ; Salt, Thomas E ; Luong, Vy ; Wood, Nicholas ; Cheung, William ; Maass, Annelie ; Ferrari, Giulio ; Russo-Marie, Françoise ; Sillito, Adam M ; Cheetham, Michael E ; Moss, Stephen E ; Fitzke, Frederick W ; Cordeiro, M. Francesca

Proceedings of the National Academy of Sciences - PNAS, 2007-08, Vol.104 (33), p.13444-13449 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
Targeting amyloid-β in glaucoma treatment
Autor: Guo, Li ; Salt, Thomas E ; Luong, Vy ; Wood, Nicholas ; Cheung, William ; Maass, Annelie ; Ferrari, Giulio ; Russo-Marie, Françoise ; Sillito, Adam M ; Cheetham, Michael E ; Moss, Stephen E ; Fitzke, Frederick W ; Cordeiro, M. Francesca
Assuntos: Aggregation ; Amyloid beta-Peptides - drug effects ; Animal models ; Animals ; Antibodies ; Apoptosis ; Biological Sciences ; Eyes ; Ganglia ; Glaucoma ; Glaucoma - drug therapy ; Glaucoma - pathology ; Histology ; Intraocular Pressure ; Male ; Rats ; Retina ; Retinal Ganglion Cells - pathology
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2007-08, Vol.104 (33), p.13444-13449
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Author contributions: L.G., T.E.S., M.E.C., S.E.M., and M.F.C. designed research; L.G., V.L., N.W., W.C., and A.M. performed research; F.R.-M., F.W.F., and M.F.C. contributed new reagents/analytic tools; L.G., N.W., W.C., A.M., G.F., and M.F.C. analyzed data; and L.G., T.E.S., A.M.S., M.E.C., S.E.M., and M.F.C. wrote the paper.
Edited by N. Avrion Mitchison, University College London, London, United Kingdom, and approved June 28, 2007
Descrição: 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.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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Targeting amyloid-β in glaucoma treatment

Guo, Li ; Salt, Thomas E ; Luong, Vy ; Wood, Nicholas ; Cheung, William ; Maass, Annelie ; Ferrari, Giulio ; Russo-Marie, Françoise ; Sillito, Adam M ; Cheetham, Michael E ; Moss, Stephen E ; Fitzke, Frederick W ; Cordeiro, M. Francesca

United States: National Academy of Sciences

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