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Frances Fan, Anna Lisa Montemari, Stefania Rossi, Giovanni Parisi, Folami Lamoke, Francesco Facchiano, Guido Ripandelli, Manuela Bartoli; Up-regulation Of Soluble Amyloid Beta And Down-regulation Of Soluble RAGE In The Vitreous Of Age-related Macular Degeneration Patients. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6423.
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The identification of aggregates of amyloid beta (A-beta) peptides in drusen has implicated these neurotoxic factors in the pathogenesis of age-related macular degeneration (ARMD). To further determine whether production of A-beta could be involved in the pathogenesis of ARMD, we have conducted proteomic studies assessing the presence of soluble amyloid beta (sA-beta) peptides and the soluble isoform of its receptor (sRAGE) as these are considered markers of disease progression in A-beta-mediated neurodegenerative diseases including Alzheimer’s disease (AD).
Western blotting, dot blot and mass spectrometry were used to assess sA-beta and sRAGE in undiluted vitreous of ARMD patients (n=12) or control patients (n=34) undergoing vitrectomy for unrelated pathologies (trauma, macular pucker and others).
Soluble A-beta was detected in the vitreous of about 30% of the patients affected by ARMD and only in 5% of the control patients. Soluble RAGE was detected in all the analyzed patients, however the ARMD patients showed a significant decrease in sRAGE levels (p<0.003) in the undiluted vitreous.
Our data show that soluble A-beta is found in the vitreous of patients affected by ARMD whereas the soluble isoform of A-beta receptor, the sRAGE, is significantly decreased. These data are in agreement with similar findings obtained in Alzheimeir’s patients, where the up-regulation of sA-beta associated with decreased levels of the sRAGE, involved in its clearance, are markers of disease progression. Thus, the obtained results further support a pathogenic role for A-beta in ARMD.
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