Targeting amyloid-β in glaucoma treatment

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

Research output: Contribution to journalArticle

227 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)13444-13449
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number33
DOIs
Publication statusPublished - Aug 14 2007

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Retinal Ganglion Cells
Amyloid
Glaucoma
Apoptosis
Retinal Diseases
Blindness
Intraocular Pressure
Alzheimer Disease
Therapeutics

Keywords

  • Combination therapy
  • Neuroprotection
  • Retinal ganglion cell apoptosis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Guo, L., Salt, T. E., Luong, V., Wood, N., Cheung, W., Maass, A., ... Cordeiro, M. F. (2007). Targeting amyloid-β in glaucoma treatment. Proceedings of the National Academy of Sciences of the United States of America, 104(33), 13444-13449. https://doi.org/10.1073/pnas.0703707104

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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 33, 14.08.2007, p. 13444-13449.

Research output: Contribution to journalArticle

Guo, L, Salt, TE, Luong, V, Wood, N, Cheung, W, Maass, A, Ferrari, G, Russo-Marie, F, Sillito, AM, Cheetham, ME, Moss, SE, Fitzke, FW & Cordeiro, MF 2007, 'Targeting amyloid-β in glaucoma treatment', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 33, pp. 13444-13449. https://doi.org/10.1073/pnas.0703707104
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. / Targeting amyloid-β in glaucoma treatment. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 33. pp. 13444-13449.
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