Background/Aims: KCNQ1OT1 regulates the expression of tissue-specific imprinted genes within the Kcnq1 domain. Imprinted genes are positive regulators of apoptosis, one of the forms of cell death related to cataract formation, and thus may provide novel therapeutic targets for cataract treatment. Here, we studied the role of non-coding RNAs(ncRNA) in cataract formation. Methods: Human lens epithelium cells (HLECs) were treated with H 2 O 2, and the expression of KCNQ1OT1 and miR-214 was detected by qRT-PCR. The expression of caspase-1 was detected using qRT-PCR, western blot and immunostaining. To confirm our findings in cell cultures, we analysed KCNQ1OT1, miR-214, and caspase-1 expression in lens anterior capsules of both cataract patients and normal controls by qRT-PCR and western blot analysis. Results: We found that the expression of KCNQ1OT1 was increased in both human cataract lens anterior capsular samples and SRA01/04 cell lines treated with H 2 O 2 . Knockdown of KCNQ1OT1 expression significantly suppressed H 2 O 2 -induced SRA01/04 cell pyroptosis in vitro, which is the critical step in cataract formation. The expression of microRNA-214 (miR-214) was also decreased in cataract lens anterior capsular tissues and H 2 O 2 -induced SRA01/04 cell lines. Knockdown of KCNQ1OT1 significantly increased the expression of miR-214. Conclusions: We demonstrated for the first time that caspase-1 is a functional downstream target of miR-214, and knockdown of KCNQ1OT1 reduced the expression of caspase-1. These results provide evidence that the KCNQ1OT1-miR-214-caspase-1 regulatory network is a novel mechanism for promoting cataract formation.

An understanding of the mechanism of cataract formation may reduce its burden on medical care worldwide. It is established that pyroptosis is associated with oxidative stress, one of the causes of cataracts, and may provide novel therapeutic targets for the treatment of cataracts. The present study therefore investigated the role of pyroptosis in cataract formation. SRA01/04 human lens epithelium cells (HLECs) were treated with H2O2 and cell viability was assessed by an MTT assay. Pyroptosis in HLECs was examined by TUNEL staining, and the expression of caspase‑1 and interleukin (IL)‑1β was determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blot analysis and immunostaining. A caspase‑1 inhibitor was used to investigate the effects of caspase‑1 downregulation. In addition, the expression of caspase‑1 and IL‑1β in lens anterior capsule tissue samples from patients with cataracts and normal controls was also analyzed by immunostaining, RT‑qPCR and western blot analysis. The results demonstrated that pyroptosis in H2O2‑treated HLECs, and the mRNA and protein expression of caspase‑1 and IL‑1β, was significantly increased compared with control cells. Furthermore, caspase‑1 and IL‑1β expression was significantly increased in cataract tissue samples compared with normal controls. When HLECs were cotreated with a caspase‑1 inhibitor and 100 µM H2O2, caspase‑1 and IL‑1β expression were decreased compared with the 100 µM H2O2‑only group. In conclusion, the results of the present study demonstrate that pyroptosis may have a role in cataract formation, and the caspase‑1 and IL‑1β pathways may be involved in this pathological process. Pyroptosis appears to be a promising target in the prevention of cataract formation.

We report the synthesis and preparation of self-assembled poly(ethylene glycol)block-poly(glycidyl methacrylate) (PEG-b-PGMA) micelles harnessing the intrinsically hydrolysable characteristics of PGMA segments for the sustained delivery of a hydrophobic natamycin by topical administration on eye. Hydrolysis of the glycidyl groups could be achieved within physiologically relevant environment, resulting in increased drug release compared to conventional non-hydrolysable counterparts. It was found that the system provides an additional driving force for drug release by generation of hydrophilic hydroxyl groups to "push" the encapsulated hydrophobic drug away from the hydrophobic domains and into the surrounding environments. In vitro and in vivo results revealed that the drug carriers (PEG-b-PGMA micelles) and the encapsulated natamycin were not cytotoxic to human corneal epithelial cells and the released drug have strong antifungal ability to Candida albicans. Importantly, sustained natamycin release from micelles leads to the reduced administration frequency of natamycin from 8 times per day to 3 times per day in fungal keratitis (FK) rabbits. Corneal morphology of keratitis was improved by the release of natamycin from the micelle observed by anterior segment optical coherence tomography (AS-OCT) and histological analysis of the cornea. These results revealed that the use of micelle enhances the loading and delivery efficiency of natamycin and subsequently promotes the drug penetration in aqueous humor and cornea. The present study demonstrates a facile method that can greatly reduce dosing frequency of natamycin administration and thus improve long-term patient compliance.

No abstract