αA-Crystallin Peptide 66SDRDKFVIFLDVKHF80 Accumulating in Aging Lens Impairs the Function of α-Crystallin and Induces Lens Protein Aggregation

The eye lens is composed of fiber cells that are filled with α-, β- and γ-crystallins. The primary function of crystallins is to maintain the clarity of the lens through ordered interactions as well as through the chaperone-like function of α-crystallin. With aging, the chaperone function of α-crystallin decreases, with the concomitant accumulation of water-insoluble, light-scattering oligomers and crystallin-derived peptides. The role of crystallin-derived peptides in age-related lens protein aggregation and insolubilization is not understood.We found that αA-crystallin-derived peptide, (66)SDRDKFVIFLDVKHF(80), which accumulates in the aging lens, can inhibit the chaperone activity of α-crystallin and cause aggregation and precipitation of lens crystallins. Age-related change in the concentration of αA-(66-80) peptide was estimated by mass spectrometry. The interaction of the peptide with native crystallin was studied by multi-angle light scattering and fluorescence methods. High molar ratios of peptide-to-crystallin were favourable for aggregation and precipitation. Time-lapse recordings showed that, in the presence of αA-(66-80) peptide, α-crystallin aggregates and functions as a nucleus for protein aggregation, attracting aggregation of additional α-, β- and γ-crystallins. Additionally, the αA-(66-80) peptide shares the principal properties of amyloid peptides, such as β-sheet structure and fibril formation.These results suggest that crystallin-derived peptides such as αA-(66-80), generated in vivo, can induce age-related lens changes by disrupting the structure and organization of crystallins, leading to their insolubilization. The accumulation of such peptides in aging lenses may explain a novel mechanism for age-related crystallin aggregation and cataractogenesis

Correlation between different Scheimpflug-based lens densitometry analysis and effective phacoemulsification time in mild nuclear cataracts

To assess the correlations between preoperative Scheimpflug-based lens densitometry and effective phacoemulsification time (EPT) in age-related nuclear cataracts.Purpose To assess the correlations between preoperative Scheimpflug-based lens densitometry and effective phacoemulsification time (EPT) in age-related nuclear cataracts. Design Retrospective consecutive study. Methods The setting was the Ophthalmology Department, Hospital de Braga, Portugal. The study population included 50 eyes (42 patients) with age-related nuclear cataracts submitted to uneventful phacoemulsification surgery. Different analysis methods of Scheimpflug-based lens densitometry were performed: Pentacam Nucleus Staging (PNS) score with an ordinal scale from 0 to 5 and three-dimensional (3D), linear and region of interest (ROI) methods, which are displayed on an absolute scale (from 0 to 100%). EPT was calculated for the cataract surgery, which was performed by the same surgeon. Correlations between lens densitometry variables and EPT were determined using Pearson or Spearman correlation coefficients according to data normality. Results There were significant correlations between EPT and average density and maximum density variables derived from the 3D (r = 0.596, p < 0.001; r = 0.632, p < 0.001, respectively) and ROI (r = 0.527, p < 0.001; r = 0.575, p < 0.001, respectively) methods. The average density was the only parameter derived from the linear analysis that showed a significant correlation with EPT (r = 0.293, p = 0.039). The PNS score did not show a significant correlation with EPT (rho = 0.124, p = 0.390). Conclusion The densitometric parameters based on the 3D method showed the highest correlations with EPT. The referred lens densitometric analysis approach may be used in preoperative assessment in order to predict EPT more efficiently in age-related nuclear cataractsinfo:eu-repo/semantics/publishedVersio