Follicular Fluid Meiosis-Activating Sterol (FF-MAS) Enhances Lens Transparency By Increasing αA-Crystallin Solubility In Cataracts.

Insolubility and aggregation of crystallins are common features in cataracts. CYP51 has been identified as a novel candidate gene for cataracts; however, its associated phenotypes remain unconfirmed. We investigated the role of FF-MAS, synthesized by CYP51, in αA-crystallin solubility and lens transparency. FF-MAS was administered to HLE-B3 cells expressing αA-crystallin (R116C) and to rats with selenite-induced cataracts. Lens transparency was assessed using slit-lamp photography. Congo red staining and transmission electron microscopy were used to analyze lens uniformity. Western blotting and immunofluorescence were employed to detect αA-crystallin aggregation. Additionally, we evaluated the effects of FF-MAS on apoptosis, antioxidant capacity, and protein homeostasis. In HLE-B3 cells, FF-MAS reduced αA-crystallin (R116C) aggregation. In rats with selenite-induced cataracts, FF-MAS increased αA-crystallin solubility, enhanced antioxidant capacity, reduced HSP90 levels, and protected α-tubulin and AQP-0, thereby improving lens uniformity and transparency. Inhibition of CYP51 by ketoconazole also led to cataract formation in rats and mice and increased apoptosis in HLE-B3 cells. Exogenous supplementation with FF-MAS inhibited these processes. FF-MAS plays a significant role in improving αA-crystallin solubility and lens transparency. Elevating FF-MAS levels may offer a novel approach to preventing and alleviating cataracts.