Purchase this article with an account.
M. Y. Wang, F. N. Ross-Cisneros, A. A. Sadun; Immunohistochemical Study of the Receptor for Advanced Glycation End Products in Alzheimer’s Disease Optic Nerves. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5385. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Several studies have suggested that the receptor for advanced glycation end products (RAGE) is a possible mediator of pathogenesis in many neurodegenerative diseases. Once ligated, RAGE can play a role in signal transduction pathways leading to amplification and perpetuation of inflammation. The purpose of this study was to characterize the presence of RAGE in optic nerves from patients with Alzheimer’s disease (AD).
We looked at formalin-fixed, paraffin-embedded 5µm sections of 24 retrobulbar optic nerves (1-3 mm from the globe) from 12 donors previously diagnosed with AD. These were compared to 24 age-matched control optic nerves from 12 individuals with no AD. Comparisons were made after staining with an antibody directed against human RAGE. The tissue sections were counterstained with hematoxylin and observed on a Zeiss Axioskop light microscope. The neural tissue of fiber bundles was examined, excluding septal connective tissue of the nerve. Neural tissue was defined as axons and glia. The intensity and localization of immunolabeling for RAGE were qualitatively graded on a scale from 0 to 3. Grade 0 was defined as no staining, Grade 1 as mild staining, Grade 2 as moderate staining, and Grade 3 as strong staining.
Immunoreactivity for RAGE in AD nerves appeared punctate and strongest in the cytoplasm of glial cells all displaying a grade 3 staining. Immunolabeling was also observed on the myelin of axons. In contrast, age-matched controls only showed mild to moderate staining (grade 1 to 2) of glial cells and myelin.
Increased presence of RAGE in AD optic nerves may point to its involvement in the neurodegenerative process of this disease. RAGE is a multi-ligand receptor binding not only to advanced glycation end products but also amyloid beta protein and other pro-inflammatory ligands. Hence, the up-regulation of RAGE in glial cells may be a response to the increased level of advanced glycation end products or other ligands. Since increased expression of RAGE is also an age-dependent process, the stronger immunoreactivity of RAGE in AD probably suggests an overlap of both processes.
This PDF is available to Subscribers Only