New insights into change of lens proteins' stability with ageing under physiological conditions

Background Age-related cataract, which presents as a cloudy lens, is the primary cause of vision impairment worldwide and can cause more than 80% senile blindness. Previous studies mainly explored the profile of lens proteins at a low concentration because of technical limitations, which could not reflect physiological status. This study focuses on protein stability changes with ageing under physiological conditions using a novel equipment, Unchained Labs (Uncle), to evaluate protein thermal stability. Methods Samples were assessed through Unchained Labs, size-exclusion chromatography, western blot and biophysics approaches including the Thioflavin T, ultraviolet and internal fluorescence. Results With age, the melting temperature value shifted from 67.8 degrees C in the young group to 64.2 degrees C in the aged group. Meanwhile, crystallin may form more isomeric oligomers and easy to be degraded in aged lenses. The spectroscopic and size-exclusion chromatography results show a higher solubility after administrated with lanosterol under the environmental stress. Conclusion We are the first to explore rabbit lens protein stability changes with ageing using biophysical methods under physiological conditions, and this study can conclude that the structural stability and solubility of lens proteins decrease with ageing. Additionally, lanosterol could aid in resolving protein aggregation, making it a potential therapeutic option for cataracts. So, this study provides cataract models for anti-cataract drug developments

Automated summary

This study used a novel equipment called Uncle to investigate the stability of lens proteins with ageing under physiological conditions. The results showed that the structural stability and solubility of lens proteins decrease with age, and crystallin may form more oligomers in aged lenses. Additionally, lanosterol was found to improve solubility under environmental stress, making it a potential therapeutic option for cataracts.