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 α‐, β‐, and γ‐crystallin can cause cataract. γD‐crystallin (hγD) is involved in the energy dissipation of absorbed UV light by energy transfer between aromatic side chains. Early UV‐B induced damage of hγD with molecular resolution is studied by solution NMR and fluorescence spectroscopy. hγD 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 hγD is remained soluble over month. Investigating isotope‐labeled hγD surrounded by eye lens extracts from cataract patients reveals very week interactions of solvent‐exposed side chains in the C‐terminal hγD domain and some remaining photoprotective properties of the extracts. Hereditary E107A hγD 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. The eye lens gets continuously exposed to UV‐B light during human lifespan. As early damage of still soluble and globular γD‐crystallin, a local unfolding of the aromatic cluster in the N‐terminal domain around tyrosine 17 and 29 can be identified by NMR spectroscopy. Eye lens extracts of cataract patients reveal some remaining photoprotective capacity.