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The neuroregenerative effects of topical decorin on the injured mouse cornea.
J Neuroinflammation. 2020 May 04; 17(1):142.JN

Abstract

BACKGROUND

The cornea is innervated with a rich supply of sensory nerves that play important roles in ocular surface health. Any injury or pathology of the corneal nerves increases the risk of dry eye disease and infection. This study aims to evaluate the therapeutic potential of topical decorin to improve corneal nerve regeneration in a mouse model of sterile epithelial abrasion injury.

METHODS

Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6 J mice to remove the corneal sensory nerves. Decorin, or vehicle, was applied topically, three times per day for 1 week or every 2 h for 6 h. Spectral-domain optical coherence tomography was performed to measure the abrasion area and corneal thickness. Wholemount immunofluorescence staining was used to assess sensory nerve regeneration (β-tubulin III) and immune cell density (CD45, Iba1, CD11c). To investigate the specific role of dendritic cells (DCs), Cx3cr1gfp/gfp mice, which spontaneously lack resident corneal epithelial DCs, were also investigated. The effect of prophylactic topical administration of recombinant human decorin (applied prior to the abrasion) was also investigated. Nerve tracing (NeuronJ software) was performed to compare recovery of basal nerve axons and superficial nerve terminals in the central and peripheral cornea.

RESULTS

At 6 h after injury, topical decorin application was associated with greater intraepithelial DC recruitment but no change in re-epithelialisation or corneal thickness, compared to the vehicle control. One week after injury, sub-basal nerve plexus and superficial nerve terminal density were significantly higher in the central cornea in the decorin-treated eyes. The density of corneal stromal macrophages in the decorin-treated eyes and their contralateral eyes was significantly lower compared to saline-treated corneas. No significant improvement in corneal nerve regeneration was observed in Cx3cr1gfp/gfp mice treated with decorin.

CONCLUSIONS

Decorin promotes corneal epithelial nerve regeneration after injury. The neuroregenerative effect of topical decorin was associated with a higher corneal DC density during the acute phase, and fewer macrophages at the study endpoint. The corneal neuroregenerative effects of decorin were absent in mice lacking intraepithelial DCs. Together, these findings support a role for decorin in DC-mediated neuroregeneration following corneal abrasion injury.

Authors+Show Affiliations

Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, 3053, Australia.Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, 3053, Australia.School of Chemical Engineering, University of Birmingham, Birmingham, B15 2TT, UK.School of Chemical Engineering, University of Birmingham, Birmingham, B15 2TT, UK.Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, Birmingham and Midland Eye Centre, Birmingham, UK. Neuroscience and Ophthalmology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK.Neuroscience and Ophthalmology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK.Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, 3053, 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, Victoria, 3053, Australia. holly.chinnery@unimelb.edu.au.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32366307

Citation

Wu, Mengliang, et al. "The Neuroregenerative Effects of Topical Decorin On the Injured Mouse Cornea." Journal of Neuroinflammation, vol. 17, no. 1, 2020, p. 142.
Wu M, Downie LE, Grover LM, et al. The neuroregenerative effects of topical decorin on the injured mouse cornea. J Neuroinflammation. 2020;17(1):142.
Wu, M., Downie, L. E., Grover, L. M., Moakes, R. J. A., Rauz, S., Logan, A., Jiao, H., Hill, L. J., & Chinnery, H. R. (2020). The neuroregenerative effects of topical decorin on the injured mouse cornea. Journal of Neuroinflammation, 17(1), 142. https://doi.org/10.1186/s12974-020-01812-6
Wu M, et al. The Neuroregenerative Effects of Topical Decorin On the Injured Mouse Cornea. J Neuroinflammation. 2020 May 4;17(1):142. PubMed PMID: 32366307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The neuroregenerative effects of topical decorin on the injured mouse cornea. AU - Wu,Mengliang, AU - Downie,Laura E, AU - Grover,Liam M, AU - Moakes,Richard J A, AU - Rauz,Saaeha, AU - Logan,Ann, AU - Jiao,Haihan, AU - Hill,Lisa J, AU - Chinnery,Holly R, Y1 - 2020/05/04/ PY - 2020/01/23/received PY - 2020/04/13/accepted PY - 2020/5/6/entrez PY - 2020/5/6/pubmed PY - 2021/3/20/medline KW - Corneal sensory nerves KW - Decorin KW - Dendritic cells KW - Immunomodulation KW - Macrophages KW - Nerve regeneration SP - 142 EP - 142 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 17 IS - 1 N2 - BACKGROUND: The cornea is innervated with a rich supply of sensory nerves that play important roles in ocular surface health. Any injury or pathology of the corneal nerves increases the risk of dry eye disease and infection. This study aims to evaluate the therapeutic potential of topical decorin to improve corneal nerve regeneration in a mouse model of sterile epithelial abrasion injury. METHODS: Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6 J mice to remove the corneal sensory nerves. Decorin, or vehicle, was applied topically, three times per day for 1 week or every 2 h for 6 h. Spectral-domain optical coherence tomography was performed to measure the abrasion area and corneal thickness. Wholemount immunofluorescence staining was used to assess sensory nerve regeneration (β-tubulin III) and immune cell density (CD45, Iba1, CD11c). To investigate the specific role of dendritic cells (DCs), Cx3cr1gfp/gfp mice, which spontaneously lack resident corneal epithelial DCs, were also investigated. The effect of prophylactic topical administration of recombinant human decorin (applied prior to the abrasion) was also investigated. Nerve tracing (NeuronJ software) was performed to compare recovery of basal nerve axons and superficial nerve terminals in the central and peripheral cornea. RESULTS: At 6 h after injury, topical decorin application was associated with greater intraepithelial DC recruitment but no change in re-epithelialisation or corneal thickness, compared to the vehicle control. One week after injury, sub-basal nerve plexus and superficial nerve terminal density were significantly higher in the central cornea in the decorin-treated eyes. The density of corneal stromal macrophages in the decorin-treated eyes and their contralateral eyes was significantly lower compared to saline-treated corneas. No significant improvement in corneal nerve regeneration was observed in Cx3cr1gfp/gfp mice treated with decorin. CONCLUSIONS: Decorin promotes corneal epithelial nerve regeneration after injury. The neuroregenerative effect of topical decorin was associated with a higher corneal DC density during the acute phase, and fewer macrophages at the study endpoint. The corneal neuroregenerative effects of decorin were absent in mice lacking intraepithelial DCs. Together, these findings support a role for decorin in DC-mediated neuroregeneration following corneal abrasion injury. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/32366307/The_neuroregenerative_effects_of_topical_decorin_on_the_injured_mouse_cornea_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-020-01812-6 DB - PRIME DP - Unbound Medicine ER -