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Choroidal neovascularization (CNV) is a major cause of vision loss in many retinal diseases. Hypoxia is determined to be a key inducer of CNV and hypoxia-inducible factor-1 (HIF-1) is an important transcription factor. Epithelial-mesenchymal transition (EMT) and the synthesis of proangiogenic cytokines make great contributions to the development of CNV. In the present study, the role of HIF-1α signaling in the regulation of angiogenin (ANG) expression and EMT in hypoxic retinal pigment epithelial cells was investigated. A significant elevation expression of ANG expression level in a mouse model of laser-induced CNV was demonstrated. In a hypoxic model of ARPE-19, an increased expression level of ANG and induction of EMT accompanied with stabilization and nucleus translocation of HIF-1α. Blockage of HIF-1α signaling resulted in inhibition of high expression of ANG and EMT features. The direct interaction between HIF-1α and ANG promoter region was identified by ChIP-qPCR. The association of RNase 4 mRNA level with HIF-1α signaling was also clarified in APRE-19. Moreover, the exogenous ANG translocated into the nucleus, enhanced 45S rRNA transcription, promoted cell proliferation and tube formation in human retinal microvascular endothelial cells. In conclusion, the hypoxic conditions regulate the expression of ANG and EMT via an activation of HIF-1α signaling. It provides molecular evidence for potential therapy strategies of treating CNV.

Fungal keratitis is one of the most common blindness-causing diseases, but clinical antifungal treatment remains a challenge. The fungal cell wall and biofilm matrix which severely confine the drug preparation are the critical obstructive factors to therapeutic effects. Herein, we report ethylenediaminetetraacetic acid (EDTA) modified AgCu2O nanoparticles (AgCuE NPs) to disrupt the cell wall and then eradicate C. albicans through the internal cascade synergistic effects of ion-released chemotherapy, chemodynamic therapy, photodynamic therapy, and mild photothermal therapy. AgCuE NPs exhibited excellent antifungal activity both in preventing biofilm formation and in destroying mature biofilms. Furthermore, AgCuE NP based gel formulations were topically applied to kill fungi, reduce inflammation, and promote wound healing, using optical coherence tomography and photoacoustic imaging to monitor nanogel retention and therapeutic effects on the infected murine cornea model. The AgCuE NP gel showed good biosafety and no obvious ophthalmic and systemic side effects. This study suggests that the AgCuE NP gel is an effective and safe antifungal strategy for fungal keratitis with a favorable prognosis and potential for clinical translation.

Purpose To compare the levels of inflammatory molecules in tear samples between patients with meibomian gland dysfunction (MGD)-related evaporative dry eye (EDE) and healthy subjects and to analyze the correlations between the levels of tear inflammatory molecules and ocular surface parameters. Methods A total of 30 MGD-related EDE patients (48 eyes) and ten healthy volunteers (15 eyes) were enrolled. Dry eye-related examinations and questionnaires were obtained from all participants. The levels of nine inflammatory molecules were determined through multiplex bead analysis. Results Inflammatory molecules including ICAM-1, IFN-γ, CXCL8/IL-8, IL-6, TNF-α and IL-12p70 were detected in 100% of the patients, while IL-1α, IL-1β and IL-10 were detected in 56.25%, 13.60% and 45.83% of the patients, respectively. Moreover, ICAM-1, IL-8, IL-6, TNF-α, IL-12p70 and IFN-γ were detected in 86.67–100% of the healthy subjects, and the detection rates of IL-10, IL-1α and IL-1β were below 50%. The levels of IL-8, IL-6, IFN-γ and ICAM-1 were significantly higher in the patient group compared with the control group. In addition, IL-8 and IL-6 were negatively correlated with Schirmer I test. Besides, IFN-γ was negatively correlated with tear film breakup time. Furthermore, ICAM-1 and IL-6 were positively correlated with meibography score. Conclusions Collectively, patients with MGD-related EDE had higher levels of inflammatory molecules in their tears, and some molecules were correlated with ocular surface parameters. These findings suggested that inflammation played an important role in MGD-related EDE, and several inflammatory molecules could be used in the diagnosis and the treatment of MGD-related EDE.

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Purpose We aimed to evaluate the efficacy of bandage contact lens (BCL) for the management of dry eye disease (DED) after cataract surgery. Methods A total of 120 patients (140 eyes) with age-related cataract and DED were enrolled in this study. Patients underwent standard micro-incision phacoemulsification surgeries and were divided into control or BCL groups. Slit-lamp biomicroscopic examination, Ocular Surface Disease Index, keratograph analysis and Schirmer I test were executed, and the levels of tear inflammatory molecules were detected. Results In the control group, the NIAvg-BUT and Schirmer I test scores were significantly decreased at 1 week post-operation compared with baseline levels (P = 0.035 and P = 0.009, respectively). In the BCL group, the NIF-BUT and Schemer I test scores were significantly improved at 1 month after operation compared with the control group (P = 0.012 and P < 0.001, respectively). Levels of IL-6, IL-8 and ICAM-1 were significantly increased in the control group at 1 month after the operation (P = 0.005, P = 0.038 and P = 0.022, respectively), while there was no difference in the BCL group. The increase in the IL-6 level in the control group was significantly higher compared with that in the BCL group (P = 0.047). In DED patients, there were significant correlations between ocular surface parameters and inflammatory molecules. Conclusions Cataract surgery could lead to the development or worsening of DED. The application of BCLs after cataract surgery could stabilize the ocular surface and tear film, improve the corneal healing and reduce the inflammation. Collectively, our findings suggested that proper use of BCLs after cataract surgery played an effective role in the management of DED. Trial registration ClinicalTrials, NCT04100031. Registered 18 September 2019—retrospectively registered