A Dual Therapeutic Approach for the Reversal of Cataracts
| Autor: | A. Pfaff, J. Beltz, N. Ercall |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
chemistry.chemical_classification
education.field_of_study Antioxidant medicine.medical_treatment Lanosterol Population General Medicine medicine.disease Biochemistry eye diseases Amino acid Ophthalmology chemistry.chemical_compound chemistry Cataracts Crystallin Physiology (medical) medicine Thiol Protein folding sense organs education |
| Zdroj: | Free Radical Biology and Medicine. 100:S80 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2016.10.197 |
| Popis: | 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, especially in developing countries where surgeons are few and access to facilities is limited. 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. Cataract is a clouding of the lens caused by the aggregation of water-soluble proteins known as crystallins. These crystallin proteins are a major component of the lens and are responsible for its ability to refract light. Crystallin proteins are rich in sulfur-containing amino acids, and are thus 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 chaperones 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, preserving the function of these chaperones. The primary objective of the following studies was to target crystallin aggregation both directly (through use of a thiol antioxidant to reduce oxidized crystallins) and indirectly (by bolstering α-crystallin stability). To investigate promising thiol antioxidant candidates for incorporation into a topical cataract treatment, HPLC analysis was conducted on topically treated male Wistar rat pup lenses to determine the bioavailability of various thiols. Selected thiol antioxidants were examined for their ability to reverse cataracts when used in combination with 25-hydroxycholesterol. |
| Databáze: | OpenAIRE |
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