Early Stage UV-B Induced Molecular Modifications of Human Eye Lens γD-Crystallin

In the human eye lenses, the crystallin proteins facilitate transparency, light refraction, as well as UV light protection. A deregulated balanced interplay between alpha-, beta-, and gamma-crystallin can cause cataract. gamma D-crystallin (h gamma D) is involved in the energy dissipation of absorbed UV light by energy transfer between aromatic side chains. Early UV-B induced damage of h gamma D with molecular resolution is studied by solution NMR and fluorescence spectroscopy. h gamma D modifications are restricted to Tyr 17 and Tyr 29 in the N-terminal domain, where a local unfolding of the hydrophobic core is observed. None of the tryptophan residues assisting fluorescence energy transfer is modified and h gamma D is remained soluble over month. Investigating isotope-labeled h gamma D surrounded by eye lens extracts from cataract patients reveals very week interactions of solvent-exposed side chains in the C-terminal h gamma D domain and some remaining photoprotective properties of the extracts. Hereditary E107A h gamma D found in the eye lens core of infants developing cataract shows under the here used conditions a thermodynamic stability comparable to the wild type but an increased sensitivity toward UV-B irradiation.

Automated summary

Crystallin proteins in the human eye lenses play a role in maintaining transparency, light refraction, and UV light protection. Imbalance in the interaction between alpha-, beta-, and gamma-crystallin can lead to cataracts. The research looks into the effects of UV-B radiation on gamma D-crystallin, specifically observing changes in the N-terminal domain. It is found that some photoprotective properties remain in extracts from cataract patients. Additionally, a genetic mutation in the eye lens core of infants with cataracts increases sensitivity to UV-B irradiation.