Glial and endothelial blood-retinal barrier responses to amyloid-β in the neural retina of the rat

Peter JB Anderson1,a, HR Watts1,a, CJ Hille3, KL Philpott3, P Clark4, M Croucher, S Gentleman2, Ling-Sun Jen11Department of Cellular and Molecular Neuroscience; 2Department of Clinical Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Charing Cross Hospital Campus, L...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Peter JB Anderson, HR Watts, CJ Hille, KL Philpott, P Clark, et al
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2008
Materias:
Acceso en línea:https://doaj.org/article/f9123dbfaa3242009c31e7f5c0b88599
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:Peter JB Anderson1,a, HR Watts1,a, CJ Hille3, KL Philpott3, P Clark4, M Croucher, S Gentleman2, Ling-Sun Jen11Department of Cellular and Molecular Neuroscience; 2Department of Clinical Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Charing Cross Hospital Campus, London, UK; 3Neurosciences, Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, Harlow, Essex, UK; 4Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, UK; aThese researchers contributed equally to this paperAbstract: The effects of an intravitreal or subretinal injection of soluble or aggregated forms of Aβ1–42 on retinal nestin-immunoreactivity (-IR) and glial fibrillary acidic protein (GFAP)-IR in astrocytes and Müller glial cells and the integrity of the blood-retinal barrier (BRB) were tested in the in vivo rat vitreal-retinal model. Retinas were exposed for 1, 2, 3, 5 or 30 days. We present novel data demonstrating that aggregated Aβ1–42 up-regulates nestin-IR in astrocytes and Müller cells, with a graded response directly related to the length of pre-injection aggregation time. Similar results were obtained with GFAP-IR, but the signal was weaker. An intravitreal injection of aggregated Aβ1–42 led to VEGF-IR up-regulation, particularly in the GCL and to a lesser extent in the INL. VEGFR1-IR (Flt1) was also increased, particularly in Müller cells and this was accompanied by marked leakage of albumin into the retinal parenchyma of the injected eye, but not in the contralateral eye.Keywords: amyloid-β, Müller cells, blood-retinal barrier