In:
Ophthalmic Research, S. Karger AG, Vol. 65, No. 1 ( 2022), p. 40-51
Abstract:
〈 b 〉 〈 i 〉 Purpose: 〈 /i 〉 〈 /b 〉 The objective of the study was to investigate efficacy and mechanisms of mouse adipose-derived mesenchymal stem cell-derived exosomes (mADSC-Exos) in the benzalkonium chloride (BAC)-induced mouse dry eye model. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Exosomes in the mADSC culture supernatant were isolated by ultracentrifugation. Western blotting, nanoparticle tracking analysis, and transmission electron microscopy were used to characterize mADSC-Exos. An experimental mouse model of dry eye was established by instillation of 0.2% BAC. mADSC-Exos were administered following BAC treatment. The positive control group was treated with commercial eye drops (0.1% pranoprofen). Corneal fluorescein staining, tear secretion, and tear film break-up time (BUT) were evaluated, and histologic analysis of the cornea and conjunctiva was performed by hematoxylin and eosin and periodic acid-Schiff staining. Apoptosis in the corneal epithelium was detected with the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and by Western blotting. Levels of pro-inflammatory cytokines in the cornea and conjunctiva were evaluated by flow cytometry, and mRNA and protein levels of NLR family pyrin domain-containing 3 (NLRP3) pathway components were assessed by quantitative real-time PCR and Western blotting, respectively. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 mADSC-Exos were characterized as vesicles with a bilayer membrane. The particle size distribution peak was at 134 nm. mADSC-Exos specifically expressed cluster of differentiation (CD)9, CD63, and CD81. mADSC-Exos treatment repaired ocular surface damage. Additionally, mADSC-Exos inhibited cell apoptosis, decreased the levels of interleukin (IL)-1β, IL-6, IL-1α, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, and increased levels of the anti-inflammatory cytokine IL-10. Meanwhile, NLRP3 inflammasome activation and upregulation of caspase-1, IL-1β, and IL-18 were reversed by mADSC-Exos. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 mADSC-Exos alleviate ocular surface inflammation, suggesting that it is a promising treatment for dry eye.
Type of Medium:
Online Resource
ISSN:
0030-3747
,
1423-0259
Language:
English
Publisher:
S. Karger AG
Publication Date:
2022
detail.hit.zdb_id:
1483177-6
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