Targeting amyloid-beta in glaucoma treatment.
The development of the devastating neurodegenerative condition, Alzheimer's disease, is strongly associated with amyloid-beta (Abeta) 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 Abeta 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 Abeta 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 Abeta pathway provides a therapeutic avenue in glaucoma management. Furthermore, our work demonstrates that the combination of agents affecting multiple stages in the Abeta pathway may be the most effective strategy in Abeta-related diseases.
Glaucoma and Retinal Degeneration Research, University College London Institute of Ophthalmology, Bath Street, London EC1V 9EL, United Kingdom.
Li
L
Guo
Thomas E
TE
Salt
Vy
V
Luong
Nicholas
N
Wood
William
W
Cheung
Annelie
A
Maass
Giulio
G
Ferrari
Françoise
F
Russo-Marie
Adam M
AM
Sillito
Michael E
ME
Cheetham
Stephen E
SE
Moss
Frederick W
FW
Fitzke
M Francesca
MF
Cordeiro
D016229:Amyloid beta-Peptides / Q000187:drug effects*; D000818:Animals; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D007429:Intraocular Pressure; D008297:Male; D051381:Rats; D012165:Retinal Ganglion Cells / Q000473:pathology
D016229:Amyloid beta-Peptides