Cyclosporin A improves the hyperosmotic response in an experimental dry eye model by inhibiting the HMGB1/TLR4/NF-κB signaling pathway.

Hyperosmolarity is closely related to dry eye disease (DED), which induces corneal epithelial cell structure and dysfunction leading to ocular surface inflammation. Cyclosporine A (CSA) is a cyclopeptide consisting of 11 deduced amino acids. It has an immunosuppressive effect and shows a vital function in inhibiting the inflammatory response. The mechanism of CSA in DED is still not entirely clear. This experiment aimed to investigate the possible mechanism of CSA in the hyperosmotic DED model. This study found that CSA can inhibit the transcript levels of DED high mobility group protein 1 (HMGB1), Toll-like receptor 4 (TLR4) and nuclear transcription factor κB (NF-κB) in signaling pathways. In addition, the study also found that 550 mOsm/L can induce the formation of DED models in vivo or in vitro. Furthermore, different concentrations of CSA have different effects on the expression of HMGB1 in human corneal epithelial cells under hyperosmotic stimulation, and high concentrations of CSA may increase the expression of HMGB1. In addition, CSA effectively reduced the corneal fluorescence staining score of the DE group and increased the tear volume of mice. Therefore, this experimental investigation might supply new evidence for the mechanism of CSA in DED, provide a potential new therapy for treating DED, and provide a theoretical basis for CSA treatment of DED.

Acute uveitis caused by abnormal glucose and lipid metabolism: a case report.

PURPOSE: This report describes a rare case of acute uveitis with severe anterior chamber inflammation due to abnormal glucose and lipid metabolism. CASE PRESENTATION: A 31-year-old male patient complained of redness in the right eye with decreased visual acuity for 3 days. Ocular examination revealed a milky white clouding of the right anterior chamber of the eye. Two clusters of yellowish-white exudates were visible on the surface of the iris in the upper nasal and temporal areas in addition to elevated intraocular pressure. He had a previous diagnosis of type 2 diabetes mellitus (T2DM). Laboratory tests suggested hyperlipidemia and ketoacidosis. After admission, topical glucocorticoids, mydriasis, and intraocular pressure-lowering drugs combined with hypoglycemic and lipid-lowering therapy and fluid replacement therapy were given immediately. After 10 days of treatment, the uveitis and systemic condition of the right eye were effectively controlled and improved. CONCLUSION: Abnormal glucose and lipid metabolism leads to impairment of the blood-aqueous barrier, which causes a severe uveitis response in the anterior chamber. After the use of topical steroids and mydriatic eye drops combined with systemic hypoglycemic and lipid-lowering interventions, the condition was significantly relieved.

MicroRNA-22-3p Regulates the Apoptosis of Lens Epithelial Cells Through Targeting KLF6 in Diabetic Cataracts.

Purpose: The purpose of this study was to identify novel abnormally expressed microRNAs (miRNAs) and their downstream target in diabetic cataract (DC). Methods: General feature, fasting blood glucose, glycosylated hemoglobin, and type A1c (HbA1c) expression level of patients were collected. DC capsular tissues were obtained from patients and the lens cells (HLE-B3) exposed to different concentrations of glucose were used to simulate the model in vitro. Both mimic and inhibitor of miR-22-3p were transferred into HLE-B3 to up- and downregulate miR-22-3p expression, respectively. The cellular apoptosis was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunofluorescence. The downstream target gene of miR-22-3p was identified by dual luciferase reporter. Results: In DC capsules and HLE-B3 under hyperglycemia, miR-22-3p showed a significant downward trend. The expression of BAX was upregulated and the BCL-2 was downregulated following high glucose. The expression of BAX was significantly down- or upregulated in HLE-B3 cells following transfection of mimic or inhibitor of miR-22-3p, respectively. Conversely, BCL-2 was significantly increased or decreased. Dual luciferase reporter assay showed that miR-22-3p directly targeted Krüppel Like Factor 6 (KLF6) to regulate cell apoptosis. In addition, the expression of KLF6 were significantly up- or downregulated following transfection of inhibitor or mimic of miR-22-3p. Conclusions: This study suggested that miR-22-3p could inhibit lens apoptosis by targeting KLF6 directly under high glucose condition. The miR-22-3p/KLF6 signal axis may provide novel insights into the pathogenesis of DC. Translational Relevance: Differential expression of miR-22-3p may account for the pathogenesis of DC and lead to a new therapeutic strategy for DC.