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Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function.

ABSTRACT: Dry eye syndrome (DES) is a chronic ocular disease that induces epithelial damage to the cornea by decreasing tear production and quality. Adequate treatment options have not been established for severe DES such as Sjogren's syndrome due to complicated pathological conditions. To solve this problem, we focused on the conditioned medium of human adipose-derived mesenchymal stem cells (hAdMSC-CM), which have multiple therapeutic properties. Here, we showed that hAdMSC-CM suppressed Benzalkonium Chloride (BAC)-induced cytotoxicity and inflammation in human corneal epithelial cells (hCECs). In addition, hAdMSC-CM increased the expression level and regulated the localisation of barrier function-related components, and improved the BAC-induced barrier dysfunction in hCECs. RNA-seq analysis and pharmacological inhibition experiments revealed that the effects of hAdMSC-CM were associated with the TGFβ and JAK-STAT signalling pathways. Moreover, in DES model rats with exorbital and intraorbital lacrimal gland excision, ocular instillation of hAdMSC-CM suppressed corneal epithelial damage by improving barrier dysfunction of the cornea. Thus, we demonstrated that hAdMSC-CM has multiple therapeutic properties associated with TGFβ and JAK-STAT signalling pathways, and ocular instillation of hAdMSC-CM may serve as an innovative therapeutic agent for DES by improving corneal barrier function.

SUBMITTER: Imaizumi T

PROVIDER: S-EPMC10421917 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function.

Imaizumi Tsutomu T Hayashi Ryuhei R Kudo Yuji Y Li Xiaoqin X Yamaguchi Kaito K Shibata Shun S Okubo Toru T Ishii Tsuyoshi T Honma Yoichi Y Nishida Kohji K

Scientific reports 20230811 1

Dry eye syndrome (DES) is a chronic ocular disease that induces epithelial damage to the cornea by decreasing tear production and quality. Adequate treatment options have not been established for severe DES such as Sjogren's syndrome due to complicated pathological conditions. To solve this problem, we focused on the conditioned medium of human adipose-derived mesenchymal stem cells (hAdMSC-CM), which have multiple therapeutic properties. Here, we showed that hAdMSC-CM suppressed Benzalkonium Ch ...[more]

PMID: 37567940

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Project description:PurposeTo investigate the impact of transmembrane protein CMTM6 on the pathogenesis of dry eye disease (DED) and elucidate its potential mechanisms.MethodsCMTM6 expression was confirmed by database analysis, real-time polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry. Tear secretion was measured using the phenol red thread test. Immune cell infiltration was assessed through flow cytometry. Barrier function was evaluated by fluorescein sodium staining, immunofluorescence staining of zonula occludens 1 (ZO-1), and electric cell-substrate impedance sensing (ECIS) assessment. For silencing CMTM6 expression, siRNA and shRNA were employed, along with lentiviral vector-mediated overexpression of CMTM6. Proinflammatory cytokine levels were analyzed by RT-PCR and cytometric bead array (CBA) analysis.ResultsCMTM6 showed high expression in healthy human and mouse corneal and conjunctival epithelium but was notably reduced in DED. Notably, this downregulation was correlated with disease severity. Cmtm6-/- dry eye (DE) mice displayed reduced tear secretion, severe corneal epithelial defects, decreased conjunctival goblet cell density, and upregulated inflammatory response. Additionally, Cmtm6-/- DE mice and CMTM6 knockdown human corneal epithelial cell-transformed (HCE-T) cells showed more severe barrier disruption and reduced expression of ZO-1. Knockdown of CMTM6 in HCE-T cells increased inflammatory responses induced by hyperosmotic stress, which was significantly mitigated by CMTM6 overexpression. Moreover, the level of phospho-p65 in hyperosmolarity-stimulated HCE-T cells increased after silencing CMTM6. Nuclear factor kappa B (NF-κB) p65 inhibition (JSH-23) reversed the excessive inflammatory responses caused by hyperosmolarity in CMTM6 knockdown HCE-T cells.ConclusionsThe reduction in CMTM6 expression on the ocular surface contributes to the pathogenesis of DED. The CMTM6-NF-κB p65 signaling pathway may serve as a promising therapeutic target for DED.

Dataset Information

Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function.

Publications

Ocular instillation of conditioned medium from mesenchymal stem cells is effective for dry eye syndrome by improving corneal barrier function.

Similar Datasets

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