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Holly Chinnery, Mengliang Wu, Laura Elizabeth Downie, Haihan Jiao, Liam Grover, Ann Logan, Kirthana Senthil, Lisa J Hill; The neuroregenerative effects of topical decorin on the injured mouse cornea.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1377.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the effect of decorin on sensory nerve regeneration and immunomodulation in a mouse model of sterile corneal epithelial abrasion.
Bilateral central corneal epithelial abrasion (2-mm, Alger Brush) was performed on young C57BL/6J mice (n=8/group) to remove the corneal sensory nerves. Decorin was applied topically 3 times per day for one week or every 2 hours for 6 hours. Spectral-domain optical coherence tomography (SD-OCT) was conducted to monitor the abrasion area and corneal thickness. Wholemount immunostaining was used to measure nerve regeneration (β-tubulin III) and immune cells (CD45, Iba1, CD11c). To investigate the role of dendritic cells (DCs), Cx3cr1gfp/gfp mice, which spontaneously lack resident corneal epithelial DCs, were included. Nerve tracing (NeuronJ; presented as sum length/84000um2) was conducted to compare recovery of subbasal nerve axons and superficial nerve terminals in the central and peripheral cornea.
At 6 hours post injury, decorin application was associated with higher peripheral intrapepithelial DCs (39.6 ± 4.3 cells/mm2 [decorin] vs 22.3 ± 2.5 cells/mm2 [saline]; P < 0.001). There was no difference in re-epithelialisation, corneal thickness, or macrophage density between groups. At one week post injury, in the central cornea of decorin-treated eyes, the sum length of the superficial nerve terminals was significantly higher (1806 ± 107.5 µm, decorin vs 1355 ± 80.9 µm, saline; P < 002), and also the subbasal nerve plexus (3238 ± 290.1 µm, decorin vs 1963 ± 218.4 µm, saline; P < 006). Corneal macrophage number was lower in decorin-treated eyes compared to saline-treated corneas (235.3 ± 13.3 cells/mm2, decorin, vs 161.3 ± 5.8 cells/mm2, saline; P < 0.001). No significant improvement in corneal nerve regeneration was observed in the Cx3cr1gfp/gfp mice treated with decorin.
Decorin promoted corneal epithelial nerve regeneration after injury. The neuroregenerative role of decorin was associated with modulation of corneal immune responses, specifically higher dendritic cell density during the acute phase, and lower macrophage number at the endpoint. The neuroregenerative effects of decorin was absent in mice lacking intraepithelial DCs, supporting a mechanism of decorin-mediated neuroimmunological modulation during corneal wound healing.
This is a 2020 ARVO Annual Meeting abstract.
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