Differential effects of interleukin-1beta and S100B on amyloid precursor protein in rat retinal neurons.

Title: Differential effects of interleukin-1beta and S100B on amyloid precursor protein in rat retinal neurons.
Authors: Anderson, PJ
Watts, HR
Jen, S
Gentleman, SM
Moncaster, JA
Walsh, DT
Jen, LS
Item Type: Journal Article
Abstract: Purpose: Interleukin-1β (IL-1β) and S100B calcium binding protein B (S100B) have been implicated in the pathogenesis of Alzheimers disease. Both are present in and around senile plaques and have been shown to increase levels of amyloid precursor protein (APP) mRNA in vitro. However, it is not known how either of these substances affects APP in vivo. Methods: We have studied the effects of IL-1β and S100B on the expression and processing of APP using a retinal-vitreal model. We have also investigated the effect of amyloid beta peptide (Aβ) on APP in the same system and the regulation of S100B production by Aβ and IL-1β from retinal glial cells. Results: Retinal ganglion cells constitutively express APP. However, after intravitreal injection of IL-1β or Aβ there was a marked reduction in APP levels as detected by Western blotting and IL-1β produced a decrease in APP immunoreactivity (IR). Nissl staining showed that the integrity of the injected retinas was unchanged after injection. Two days after S100B injection, there was a small reduction in APP-IR but this was accompanied by the appearance of some intensely stained large ganglion cells and there was some up-regulation in APP holoprotein levels on Western blot. Seven days post-S100B injection, these large, highly stained cells had increased in number throughout the retina. Injection of Aβ and IL-1β also caused an increase in S100B production within the retinal Müller glial cells. Conclusion: These results support the hypothesis that S100B (a glial-derived neurotrophic factor) and IL-1β (a pro-inflammatory cytokine) can modulate the expression and processing of APP in vivo and so may contribute to the progression of Alzheimers disease. © 2009 Anderson et al, publisher and licensee Dove Medical Press Ltd.
Issue Date: 1-Dec-2009
URI: http://hdl.handle.net/10044/1/18256
DOI: http://dx.doi.org/10.2147/OPTH.S2684
ISSN: 1177-5467
Start Page: 235
End Page: 242
Journal / Book Title: Clin Ophthalmol
Volume: 3
Copyright Statement: © 2009 Anderson et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
Conference Place: New Zealand
Appears in Collections:Division of Surgery
Department of Medicine



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