Amyloid-beta peptide is toxic to neurons in vivo via indirect mechanisms.
We have studied the neurotoxicity of amyloid-beta (Abeta) after a single unilateral intravitreal injection. Within the retina apoptotic cells were seen throughout the photoreceptor layer and the inner nuclear layer but not in the ganglion cell layer at 48 h after injection of Abeta(1-42) compared to vehicle control and control peptide. At 5 months, there was a significant reduction in total cell numbers in the ganglion cell layer in Nissl stained retinas. There was glial cell dysfunction with upregulation of glial fibrillary acidic protein and a reduction in the expression of Müller cell associated proteins in the injected retinas. These results suggest an indirect cytotoxic effect of Abeta on retinal neurons and an important role for dysfunction of Müller glia in mediating Abeta neurotoxicity.
Walsh
Desmond T
DT
Department of Neuroinflammation, Division of Neuroscience and Psychological Medicine, London, W6 8RF, United Kingdom.
Montero
Rosa M
RM
Bresciani
Laura G
LG
Jen
Angela Y T
AY
Leclercq
Pascale D
PD
Saunders
Debbie
D
EL-Amir
Ahmed N
AN
Gbadamoshi
Lukemann
L
Gentleman
Stephen M
SM
Jen
Ling-Sun
LS
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D005260:Female; D007267:Injections; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014822:Vitreous Body
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)