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The effect of topical decorin on temporal changes to corneal immune cells after epithelial abrasion.
J Neuroinflammation. 2022 Apr 12; 19(1):90.JN

Abstract

BACKGROUND

Corneal immune cells interact with corneal sensory nerves during both homeostasis and inflammation. This study sought to evaluate temporal changes to corneal immune cell density in a mouse model of epithelial abrasion and nerve injury, and to investigate the immunomodulatory effects of topical decorin, which we have shown previously to promote corneal nerve regeneration.

METHODS

Bilateral corneal epithelial abrasions (2 mm) were performed on C57BL/6J mice. Topical decorin or saline eye drops were applied three times daily for 12 h, 24 h, 3 days or 5 days. Optical coherence tomography imaging was performed to measure the abrasion area. The densities of corneal sensory nerves (β-tubulin III) and immune cells, including dendritic cells (DCs; CD11c+), macrophages (Iba-1+) and neutrophils (NIMP-R14+) were measured. Cx3cr1gfp/gfp mice that spontaneously lack resident corneal intraepithelial DCs were used to investigate the specific contribution of epithelial DCs. Neuropeptide and cytokine gene expression was evaluated using qRT-PCR at 12 h post-injury.

RESULTS

In decorin-treated corneas, higher intraepithelial DC densities and lower neutrophil densities were observed at 24 h after injury, compared to saline controls. At 12 h post-injury, topical decorin application was associated with greater re-epithelialisation. At 5 days post-injury, corneal stromal macrophage density in the decorin-treated and contralateral eyes was lower, and nerve density was higher, compared to eyes treated with saline only. Lower expression of transforming growth factor beta (TGF-β) and higher expression of CSPG4 mRNA was detected in corneas treated with topical decorin. There was no difference in corneal neutrophil density in Cx3cr1gfp/gfp mice treated with or without decorin at 12 h.

CONCLUSIONS

Topical decorin regulates immune cell dynamics after corneal injury, by inhibiting neutrophils and recruiting intraepithelial DCs during the acute phase (< 24 h), and inhibiting macrophage density at the study endpoint (5 days). These immunomodulatory effects were associated with faster re-epithelialisation and likely contribute to promoting sensory nerve regeneration. The findings suggest a potential interaction between DCs and neutrophils with topical decorin treatment, as the decorin-induced neutrophil inhibition was absent in Cx3cr1gfp/gfp mice that lack corneal epithelial DCs. TGF-β and CSPG4 proteoglycan likely regulate decorin-mediated innate immune cell responses and nerve regeneration after injury.

Authors+Show Affiliations

Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, Australia.Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, Australia.School of Biomedical Sciences, Institute of Clinical Sciences, University of Birmingham, Birmingham, B15 2TT, UK.Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, Australia. holly.chinnery@unimelb.edu.au.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35414012

Citation

Wu, Mengliang, et al. "The Effect of Topical Decorin On Temporal Changes to Corneal Immune Cells After Epithelial Abrasion." Journal of Neuroinflammation, vol. 19, no. 1, 2022, p. 90.
Wu M, Downie LE, Hill LJ, et al. The effect of topical decorin on temporal changes to corneal immune cells after epithelial abrasion. J Neuroinflammation. 2022;19(1):90.
Wu, M., Downie, L. E., Hill, L. J., & Chinnery, H. R. (2022). The effect of topical decorin on temporal changes to corneal immune cells after epithelial abrasion. Journal of Neuroinflammation, 19(1), 90. https://doi.org/10.1186/s12974-022-02444-8
Wu M, et al. The Effect of Topical Decorin On Temporal Changes to Corneal Immune Cells After Epithelial Abrasion. J Neuroinflammation. 2022 Apr 12;19(1):90. PubMed PMID: 35414012.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of topical decorin on temporal changes to corneal immune cells after epithelial abrasion. AU - Wu,Mengliang, AU - Downie,Laura E, AU - Hill,Lisa J, AU - Chinnery,Holly R, Y1 - 2022/04/12/ PY - 2021/11/10/received PY - 2022/03/24/accepted PY - 2022/4/13/entrez PY - 2022/4/14/pubmed PY - 2022/4/15/medline KW - Cornea KW - Decorin KW - Dendritic cells KW - Macrophages KW - Nerve regeneration KW - Neutrophils KW - Small leucine-rich proteoglycan KW - Wound healing SP - 90 EP - 90 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 19 IS - 1 N2 - BACKGROUND: Corneal immune cells interact with corneal sensory nerves during both homeostasis and inflammation. This study sought to evaluate temporal changes to corneal immune cell density in a mouse model of epithelial abrasion and nerve injury, and to investigate the immunomodulatory effects of topical decorin, which we have shown previously to promote corneal nerve regeneration. METHODS: Bilateral corneal epithelial abrasions (2 mm) were performed on C57BL/6J mice. Topical decorin or saline eye drops were applied three times daily for 12 h, 24 h, 3 days or 5 days. Optical coherence tomography imaging was performed to measure the abrasion area. The densities of corneal sensory nerves (β-tubulin III) and immune cells, including dendritic cells (DCs; CD11c+), macrophages (Iba-1+) and neutrophils (NIMP-R14+) were measured. Cx3cr1gfp/gfp mice that spontaneously lack resident corneal intraepithelial DCs were used to investigate the specific contribution of epithelial DCs. Neuropeptide and cytokine gene expression was evaluated using qRT-PCR at 12 h post-injury. RESULTS: In decorin-treated corneas, higher intraepithelial DC densities and lower neutrophil densities were observed at 24 h after injury, compared to saline controls. At 12 h post-injury, topical decorin application was associated with greater re-epithelialisation. At 5 days post-injury, corneal stromal macrophage density in the decorin-treated and contralateral eyes was lower, and nerve density was higher, compared to eyes treated with saline only. Lower expression of transforming growth factor beta (TGF-β) and higher expression of CSPG4 mRNA was detected in corneas treated with topical decorin. There was no difference in corneal neutrophil density in Cx3cr1gfp/gfp mice treated with or without decorin at 12 h. CONCLUSIONS: Topical decorin regulates immune cell dynamics after corneal injury, by inhibiting neutrophils and recruiting intraepithelial DCs during the acute phase (< 24 h), and inhibiting macrophage density at the study endpoint (5 days). These immunomodulatory effects were associated with faster re-epithelialisation and likely contribute to promoting sensory nerve regeneration. The findings suggest a potential interaction between DCs and neutrophils with topical decorin treatment, as the decorin-induced neutrophil inhibition was absent in Cx3cr1gfp/gfp mice that lack corneal epithelial DCs. TGF-β and CSPG4 proteoglycan likely regulate decorin-mediated innate immune cell responses and nerve regeneration after injury. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/35414012/The_effect_of_topical_decorin_on_temporal_changes_to_corneal_immune_cells_after_epithelial_abrasion_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-022-02444-8 DB - PRIME DP - Unbound Medicine ER -