title: Amyloid-beta peptide is toxic to neurons in vivo via indirect mechanisms.
abstract: 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.
authors.affiliation: Department of Neuroinflammation, Division of Neuroscience and Psychological Medicine, London, W6 8RF, United Kingdom.
authors.forename: Desmond T
authors.initials: DT
authors.lastname: Walsh
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Montero
authors.forename: Laura G
authors.initials: LG
authors.lastname: Bresciani
authors.forename: Angela Y T
authors.initials: AY
authors.lastname: Jen
authors.forename: Pascale D
authors.initials: PD
authors.lastname: Leclercq
authors.forename: Debbie
authors.initials: D
authors.lastname: Saunders
authors.forename: Ahmed N
authors.initials: AN
authors.lastname: EL-Amir
authors.forename: Lukemann
authors.initials: L
authors.lastname: Gbadamoshi
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Gentleman
authors.forename: Ling-Sun
authors.initials: LS
authors.lastname: Jen
mesh_terms: 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
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)