amyloid-beta-peptides and Cataract

To investigate the levels and clinical relevance of serum β-amyloid (Aβ) in age-related cataract (ARC) patients. In the present study, an overall of 402 ARC patients and 450 normal controls were recruited between June 2018 and December 2019. Serum Aβ1-40 and Aβ1-42 concentrations were assessed by Elisa. The ARC patients were further grouped into several subgroups according to gender, age, types of ARC, and degree of lens opacity. The association of Aβ levels with ARC was determined using logistic regression models. ARC patients had significantly higher serum Aβ1-40 and Aβ1-42 levels than normal control. A similar finding was observed in subjects aged over 60 years. Serum Aβ concentrations were significant correlated with the degrees of lens opacity in C-ARC and N-ARC subjects. Logistic regression analyses revealed that serum Aβ1-40 (ORs = 1.202, 95% CI 1.077 to 1.341) and Aβ1-42 (ORs = 1.686, 95% CI 1.351 to 2.103) levels were potential risk factors for ARC. ARC patients have higher serum Aβ1-40, as well as Aβ1-42 levels, which may reflect an association between Aβ and ARC pathogenesis. Serum Aβ1-42 and Aβ1-40 levels are potential risk factors for ARC.

Topics: Age Factors; Aged; Amyloid beta-Peptides; Cataract; Female; Humans; Male; Middle Aged; Peptide Fragments

Alzheimer's disease (AD) and cataract represent two common protein misfolding diseases closely associated with aging. Growing evidence suggests that these two diseases may be interrelated with each other through cross-sequence interactions between β-amyloid (Aβ) peptide and the short aggregating peptides derived from proteolytic breakdown of α-crystallin. αΑ(66-80) is one of several peptides produced by the proteolytic breakdown of α-crystallin in aged eye lens. Although it is evident that the Aβ(1-40) and αΑ(66-80) coexist in aged eye lenses and both the peptides are known to form macromolecular assemblies, their cross-sequence interaction and the seeding behavior are not known. In this study, the aggregation behavior of αΑ(66-80) has been examined in the presence of Aβ(1-40) on using thioflavin T (ThT) based aggregation kinetics. The presence of monomeric Aβ(1-40) augmented the aggregation kinetics of αΑ(66-80) and reduced the lag time of αΑ(66-80) aggregation. However, the addition of Aβ(1-40) or αΑ(66-80) fibrils (seeds) didn't result in any change in the rate of αΑ(66-80) aggregation. In this in vitro study, we could show that the presence Aβ(1-40) has substantial effect on the aggregation of αΑ(66-80), which suggests a possible interaction between AD and cataract pathologies.

Topics: Amyloid beta-Peptides; Cataract; Crystallins; Humans; Peptide Fragments; Protein Aggregation, Pathological

We investigated whether amyloid beta(Abeta) aggregates have transforming growth factor beta- like cytokine activity and cause transdifferentiation of lens epithelial cells, leading to certain types of cataract. In order to mimic Abetaaggregates, Abeta-(1-40) was crosslinked to bovine serum albumin (BSA) with disuccinimidyl suberate according to a previously described procedure. When human lens epithelial B-3 (HLE B-3) cells were treated with the Abeta-(1-40)-BSA conjugates, we observed the translocation of Smad-3, as well as the induced mRNA levels of fibronectin (FN), collagen type I (Col I), smooth muscle actin (SMA) and matrix metalloproteinase-2 (MMP-2). In addition, we investigated the morphology of rat whole lens cultured for 5 days in the presence of Abeta-(1-40)-BSA, and the immunohistochemical localizations of Abeta-(1-40)/amyloid precursor protein (APP) in human clinical tissues beneath the anterior capsules. In rat whole lens cultures, treatment with Abeta-(1-40)-BSA produced a transformed morphology that had multiple layers of lens epithelial cells. To compare the anterior capsules in anterior subcapsular cataracts with those in nuclear cataracts, immunohistochemical studies of Abeta/APP in human clinical tissues revealed that the predominant immunostaining of Abeta occurs in the anterior epithelial plaques, which likely produces the abnormal extracellular matrix. Thus, these findings suggest that Abeta aggregates in vivo are possibly involved in the regulatory process by which lens epithelial cells may transdifferentiate into fibroblast-like cells, as well as help understand the mechanisms which lead to certain types of cataractogenesis.

Topics: Amyloid beta-Peptides; Animals; Cataract; Cell Differentiation; Cell Line; Epithelial Cells; Humans; Lens, Crystalline; Peptide Fragments; Rats; Serum Albumin, Bovine