Aggregation inhibitory effect of vitamin C on cataract-associated P23T γD-crystallin.

Abstract

Cataract is a progressive loss of eye lens transparency, as a result of age-related chemical modifications or due to congenital mutations in crystallins. A vital antioxidant in the aqueous humor, the vitamin C, has been suggested to hold potential for the prophylaxis of age-related cataract. However, the effect of vitamin C on congenital cataract has not yet been investigated. Here, we explored the aggregation inhibitory effect of vitamin C on the P23T human γD-crystallin mutant, associated with congenital cataract. The effect of vitamin C on the aggregation propensity of P23T human γD-crystallin was investigated by solution NMR, atomic force microscopy (AFM), and other biophysical techniques. We found that vitamin C is able to prevent and reverse P23T human γD-crystallin aggregation in a dose-dependent manner. In particular, NMR data suggest that the inhibitory effect of vitamin C on P23T human γD-crystallin phase-separation is probably mediated by interacting with aggregation prone regions. AFM images of P23T human γD-crystallin under native aggregating conditions revealed the appearance of amorphous aggregates, that disassemble into monomers in the presence of vitamin C. The current study highlights and confirms the possibility that vitamin C is able to dissolve crystallin aggregates, potentially slowing the onset or reversing cataract.