A dual therapeutic approach for the reversal of cataracts

Purpose Over 20 million people suffer from cataracts worldwide. Currently, surgery is the only effective treatment for this condition. Although cataract surgery is routine and generally considered safe, it is neither feasible nor accessible for much of the world's population. Thus, there is a high demand for an effective topical treatment that can reverse or prevent cataracts in those for whom surgery is not a viable option. Clouding of the lens is caused by the aggregation of water‐soluble crystallin proteins. Crystallins are a major component of the lens and allow it to refract light. Crystallins are rich in sulfur‐containing amino acids, which are susceptible to the formation of disulfide bonds upon oxidative damage. This damage results in protein misfolding and aggregation. Thiol antioxidants have the potential to protect these proteins from oxidative damage and to prevent the formation of cataracts. α‐Crystallins act as chaperons for other crystallin isoforms, binding damaged β‐ and γ‐crystallins and impeding aggregation. Recently, sterols such as lanosterol and 25‐hydroxycholesterol have demonstrated the ability to stabilize the healthy, functional α‐crystallin structure, which preserves the anti‐aggregation action of these chaperons. The objective of this study was to determine additive and/or synergistic effects of a thiol antioxidant in combination with 25‐hydroxycholesterol to combat crystallin aggregation in two ways: protecting crystallin thiol residues and bolstering α‐crystallin chaperon activity. Methods To investigate thiol antioxidant candidates for incorporation into a topical cataract treatment, an ex vivo model using Wistar rat pup lenses was employed. Various thiol antioxidants were examined for their ability to reverse cataracts when used in combination with 25‐hydroxycholesterol. Results To be discussed. Conclusions To be discussed.