Abstract
Purpose :
Decorin imparts a neuroregenerative effect that is associated with immune cell alterations in injured corneas. This study aims to explore the dynamic changes of corneal immune cell density (dendritic cells, macrophages and neutrophils) after topical application of decorin in a mouse model of sterile epithelial abrasion.
Methods :
Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6J mice (n = 8). Decorin, or saline, was applied topically on right or left eye respectively , three times per day for one or five days. A control group (n = 8) with application of saline on both eyes was also included. Wholemount immunofluorescence staining and confocal microscopy was used to assess corneal immune cell density (CD45, Iba1, CD11c, NIMP) in the central and peripheral cornea. Cells were counted manually using ImageJ software. Data were analysed by fitting a linear mixed-effects model using restricted maximum likelihood (REML) and Kenward-Roger tests for fixed effects.
Results :
At 1 day after injury, compared to the saline-treated control eyes, greater intraepithelial DC recruitment was observed in decorin-treated eyes (central: 13.2±5.7 VS 7.7±4.0 cells/mm2, p = 0.010; peripheral: 23.8±6.2 VS 18.2±4.2 cells/mm2, p = 0.009) but not contralateral eyes. At 5 days after injury, there was no difference between groups. The density of macrophages was similar in all groups at 1 day, but was significantly lower in the decorin-treated eyes and contralateral eyes at 5 days post-injury (central: 125.1±19.2 [Decorin-treated eyes] and 156.6±25.0 [Contralateral eyes] VS 180.7±28.3 cells/mm2 [saline-treated eyes], p < 0.001 and p = 0.041; peripheral: 114.4±16.1 [Decorin-treated eyes] and 133.3±22.9 [Contralateral eyes] VS 159.8±26.8 cells/mm2 [saline-treated eyes], p = 0.001 and 0.026). Relative to saline treated eyes, there was a lower density of central corneal neutrophils in decorin-treated eyes at 1 day after injury (155.4±68.2 VS 235.2±82.2 cells/mm2, p = 0.041).
Conclusions :
Topical decorin treatment was associated with a higher DC density, and less neutrophils during the acute phase after corneal injury, and fewer macrophages after 5 days. The contralateral effect of decorin on macrophage, but not DCs, indicates there may be different mechanisms for decorin-induced immunomodulation during corneal wound healing.
This is a 2021 ARVO Annual Meeting abstract.