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L.E. Goldstein, R. Moir, R. Cherny, R. Pineda, E. Blakely, P. Chang, K. Bjornstad, R. Tanzi, A. Bush, L.T. Chylack Jr; Expression and Further Characterization of Alzheimer's Disease Beta-amyloid (Abeta) in Human Aqueous Humor and Lens . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3488.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously identified and characterized Alzheimer's disease beta-amyloid (Abeta) in the human lens. Here we identify Abeta in human aqueous humor and further characterize Abeta expression and beta-amyloid precursor protein (APP) processing in human lens cells. Methods: We obtained primary aqueous humor (AH) from consenting patients undergoing cataract surgery and postmortem AH, lens, iris, cornea, retina, and vitreous from donor eyes obtained through collaboration with the MA Alzheimer's Disease Research Center. Postmortem Alzheimer's disease (AD) and control donors were evaluated by neuropathological examination. Abeta identification and characterization was conducted by western blot, tryptic digest/LC-MS sequencing, anti-Abeta SELDI-MS, and ELISA assays. APP processing was evaluated in B3 human lens epithelial cell line (Andley, et al.  IOVS 35(7):3094) and in non-immortalized human lens epithelial cells differentiated in vitro (Blakely, et al.  IOVS 41(12):3898). We also performed immunogold EM, immunohistochemistry, immunohistofluorecence, metal histochemistry, and aggregation studies. Results: We corroborated our previous identification of Abeta in the human lens and determined that expression of this peptide is increased in AD. We identified Abeta in primary and postmortem AH at a peptide concentration comparable to that determined for cerebrospinal fluid. Conditioned medium obtained from immortalized and non-immortalized human lens epithelial cells contains Abeta. Lens epithelial cells internalize Abeta and alpha2-macroglobulin (A2M) through LDL receptor-related protein (LRP)-mediated mechanisms. APP processing and Abeta expression are altered during differentiation of non-immortalized human lens epithelial cells in vitro. In the intact lens, Abeta accumulates with metal in the same deep cortical and supranuclear lens subregion. Conclusions: Abeta is expressed in human lens and aqueous humor. APP processing and Abeta expression are altered during lens epithelial differentiation, factors that may contribute to the accumulation of cytosolic Abeta within the deep cortical and supranuclear subregions of AD lenses.
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