Corneal injury (CI) affects corneal integrity and transparency, deteriorating the patient’s quality of life. This study aimed to explore the molecular mechanisms by which exosomes secreted from human umbilical cord mesenchymal stem cells (hucMSC-Exos) affect autophagy in human corneal epithelial cells (HCECs) and CI models. We isolated and identified hucMSC-Exos using nanoparticle tracking analysis, transmission electron microscopy, and western blotting. The effects of hucMSC-Exos combined with autophagy regulators on HCECs and CI mice were assessed using cell viability assays, scratch assay, cell cycle assay, apoptosis assay, corneal fluorescein staining, haze grades, pathological examinations, western blotting, and quantitative polymerase chain reaction (qPCR). In vitro results indicated that hucMSC-Exos combined with the autophagy activator had positive effects in promoting the cell proliferation, migration capacity, and the cell cycle by upregulating the proportions of cells in the S phase and the expression of PCNA, Cyclin A, Cyclin E, and CDK2. Meanwhile, the combination treatment reduced the apoptotic rate of HCECs. In vivo results indicated that hucMSC-Exos especially combined them with the autophagy activator significantly alleviated corneal epithelial defects and stromal opacity, reduced the levels of the apoptotic markers Bax and cleaved Caspase-3, reduced the inflammatory response products TNF-α, IL-1β, IL-6, and CXCL-2, and increased the Bcl-2. This was achieved by upregulating pAMPK/AMPK and pULK1/ULK1 ratios, and Beclin-1 and LC3B II/I, and by downregulating the pmTOR/mTOR ratio and p62. In contrast, clinical indications, apoptosis, and inflammation were aggravated after the application of the autophagy inhibitor. HucMSC-Exos combined with an autophagy activator significantly enhanced HCECs functions and alleviated corneal defects, apoptosis, and inflammation by activating the autophagy signaling pathway, AMPK-mTOR-ULK1, providing a new biological therapy for corneal wound healing and ocular surface regeneration.

Background Ocular surface and retinal diseases are widespread problems that cannot be ignored in today’s society. However, existing prevention and treatment still have many shortcomings and limitations, and fail to effectively hinder the occurrence and development of them. Main body The purpose of this review is to give a detailed description of the potential mechanism of exosomes and autophagy. The eukaryotic endomembrane system refers to a range of membrane-bound organelles in the cytoplasm that are interconnected structurally and functionally, which regionalize and functionalize the cytoplasm to meet the needs of cells under different conditions. Exosomal biogenesis and autophagy are two important components of this system and are connected by lysosomal pathways. Exosomes are extracellular vesicles that contain multiple signaling molecules produced by multivesicular bodies derived from endosomes. Autophagy includes lysosome-dependent degradation and recycling pathways of cells or organelles. Recent studies have revealed that there is a common molecular mechanism between exosomes and autophagy, which have been, respectively, confirmed to involve in ocular surface and retinal diseases. Conclusion The relationship between exosomes and autophagy and is mostly focused on fundus diseases, while a deeper understanding of them will provide new directions for the pathological mechanism, diagnosis, and treatment of ocular surface and retinal diseases.

AIM: To investigate thickness characteristics and vascular plexuses in retinas with reticular pseudodrusen (RPD) as an early detection strategy for age-related macular degeneration (AMD). METHODS: This retrospective study included 24 subjects (33 eyes) with RPD and 25 heathy control subjects (34 eyes). The superficial capillary plexus (SCP) and the deep capillary plexus (DCP) of the retinal posterior poles were investigated with optical coherence tomography angiography (OCTA). Retinal thicknesses and vessel densities were analyzed statistically. RESULTS: The general retinal thicknesses of RPD eyes were significantly decreased (95%CI -14.080, -0.655; P=0.032). The vessel densities of DCP in RPD eyes were significantly increased in the global (95%CI 1.067, 7.312; P=0.027), parafoveal (95%CI 0.417, 5.241; P=0.022), and perifoveal (95%CI 0.181, 6.842; P=0.039) quadrants. However, the vessel densities of the SCP were rarely increased in the eyes with RPD. CONCLUSION: The thinning of retinas in the RPD group suggests a reduction in the number of cells. Additionally, the increased vessel density of the DCP in retinas with RPD indicates a greater demand for blood supply, possibly due to the hypoxia induced RPD compensation caused by RPD in the outer retina. This study highlights the pathological risks associated with RPD and emphasizes the importance of early intervention to retard the progression of AMD.

BackgroundFungal keratitis is a common blinding eye disease, and Fusarium is one of the main species that cause fungal keratitis. As is well known, oxidative stress plays an important role in Fusarium keratitis and it is also a significant initiating factor of ferroptosis. But the relationship between Fusarium keratitis and ferroptosis is currently unclear. This study aimed to speculate and validate potential ferroptosis-related genes in Fusarium keratitis using bioinformatics analysis, which provided ideas for further research on its specific mechanism and new targets for its treatment. MethodsThe microarray expression profiling dataset (GSE58291) came from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were obtained by the limma package of the R software. The DEGs were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Then, the DEGs were intersected with the genes in the ferroptosis database. The top 5 hub genes were obtained by the protein-protein interaction (PPI) network analysis and the cytoHubba plug-in of Cytoscape software. The hub genes were subjected to GSEA analysis. Then we analyzed the immune infiltration of the samples by CIBERSORT and ssGSEA algorithm. Finally, we validated the mRNA of hub genes by qPCR.ResultsA total of 1,368 DEGs were identified and 26 ferroptosis-related DEGs were obtained. At the same time, ferroptosis-related pathways were enriched by GO and KEGG using DEGs. HMOX1, CYBB, GPX2, ALOX5 and SRC were obtained by the PPI network analysis and the cytoHubba plug-in of Cytoscape software. The iron metabolism and immune response related pathways were enriched using GSEA. They included hematopoietic cell lineage, lysosome and FC gamma R mediated phagocytosis. T cells follicular helper, monocytes, macrophages and mast cells might play an important role in Fusarium keratitis using analysis of immune infiltration. Finally, qPCR confirmed that the expression of HMOX1, CYBB, ALOX5 mRNA in the DON group was significantly elevated, while the expression of GPX2 were significantly decreased.ConclusionsFerroptosis may play an important role in Fusarium keratitis. HMOX1, CYBB, ALOX5 and GPX2 may be key ferroptosis-related genes in the pathogenesis of Fusarium keratitis.

BackgroundMyopia is one of the major public health problems worldwide. However, the exact pathogenesis of myopia remains unclear. This study proposes using voxel-based morphometry (VBM) to investigate potential morphological alterations in gray matter volume (GMV) in form-deprivation myopia (FDM) rats.MethodsA total of 14 rats with FDM (FDM group) and 15 normal controls (NC group) underwent high-resolution magnetic resonance imaging (MRI). Original T2 brain images were analyzed using VBM method to identify group differences in GMV. Following MRI examination, all rats were perfused with formalin, and immunohistochemical analysis of NeuN and c-fos levels was performed on the visual cortex.ResultsIn the FDM group, compared to the NC group, significantly decreased GMVs were found in the left primary visual cortex, left secondary visual cortex, right subiculum, right cornu ammonis, right entorhinal cortex and bilateral molecular layer of the cerebellum. Additionally, significantly increased GMVs were found in the right dentate gyrus, parasubiculum, and olfactory bulb.ConclusionsOur study revealed a positive correlation between mGMV and the expression of c-fos and NeuN in the visual cortex, suggesting a molecular relationship between cortical activity and macroscopic measurement of visual cortex structural plasticity. These findings may help elucidate the potential neural pathogenesis of FDM and its relationship to changes in specific brain regions.