Honokiol Attenuates Choroidal Neovascularization by Inhibiting the Hypoxia-Inducible Factor-α/Vascular Endothelial Growth Factor Axis via Nuclear Transcription Factor-Kappa B Activation.

PURPOSE: Honokiol is a lignan isolated from Magnolia officinalis and exhibits anti-angiogenic properties. This study was conducted to investigate the role of honokiol in choroidal neovascularization. METHODS: C57BL/6 mice were treated with honokiol at 10-20 mg/kg by daily intraperitoneal injection from day 1 to 6 after laser photocoagulation. ARPE-19 cells were cultured under hypoxic conditions with or without the presence of honokiol. After laser photocoagulation and honokiol treatment, hematoxylin and eosin staining, immunofluorescence and fundus fluorescein angiography were used to analyze the effect of honokiol on choroidal neovascularization formation. Quantitative real-time PCR, western blot, enzyme-linked immunosorbent assay, immunofluorescence, luciferase assay, and chromatin immunoprecipitation were performed to explore the mechanism of honokiol in the pathological process of choroidal neovascularization. Finally, the role of honokiol on the human choroidal vascular endothelial cells was detected by using 5-ethynyl-20-deoxyuridine assay, Transwell and Tube formation assays. RESULTS: The results of hematoxylin and eosin staining and immunofluorescence suggested that honokiol reduced the thickness, length, and area of choroidal neovascularization lesions in laser-induced choroidal neovascularization mouse model. Fundus fluorescein angiography showed that choroidal neovascularization leakage was reduced in honokiol group and the concentration of 20 mg/kg showed better effects. Mechanism studies have shown that honokiol exerted inhibitory effects on choroidal neovascularization by inactivating hypoxia-inducible factor-1α/vascular endothelial growth factor axis through the nuclear transcription factor-kappa B signaling pathway. The same results were obtained in ARPE-19 cells under hypoxic conditions. Furthermore, the conditional medium of retinal pigmented epithelial cells promoted the proliferation, migration, and tube formation of human choroidal vascular endothelial cells, while honokiol reversed these. CONCLUSION: We demonstrated that honokiol attenuated choroidal neovascularization formation by inactivating the hypoxia-inducible factor-1α/vascular endothelial growth factor axis through nuclear transcription factor-kappa B signaling pathway.

Genome-Wide Repertoire of Transfer RNA-Derived Fragments in a Mouse Model of Age-Related Cataract.

PURPOSE: To investigate the roles of tRNA-derived small RNAs (tsRNAs) containing transfer RNA-derived fragments (tRFs) and tRNA halves in age-related cataracts (ARCs). METHODS: Lens capsule tissue from Emory mice at 3 months and 8 months of age were dissected for integrated tsRNA and gene transcriptome sequencing. A quantitative real-time PCR assay (qRT-PCR) was performed for validating sequencing results. Bioinformatics analysis was constructed to reveal the roles of tsRNAs. RESULTS: A total of 422 differential expression (DE) tsRNAs were changed, in which 156 were elevated while 266 were declined in 8-month-old mice. Subsequently, the gene sequencing data exhibited 375 upregulated and 456 downregulated DE genes. Validation by qRT-PCR in 5 selected upregulated tRFs was consistent with tsRNAs sequencing results. Moreover, bioinformatics analysis identified 25 downregulated target genes of the 5 validated tRFs. Furthermore, GO analysis revealed that these target genes were mainly enriched in camera-type eye development, sensory organ development, and so on. CONCLUSION: Our study provides a novel perspective on the role of tsRNAs in the pathogenesis of ARC, and thus therapeutic potential targets for ARC.