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An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse
Published on: April 7, 2014
Modulation of the early inflammatory microenvironment in the alkali-burned eye by systemically administered
Eliska Javorkova1, Peter Trosan, Alena Zajicova
11 Institute of Experimental Medicine, Academy of Sciences of the Czech Republic , Prague, Czech Republic .
Abstract:
The aim of this study was to investigate the effects of systemically administered bone-marrow-derived mesenchymal stromal cells (MSCs) on the early acute phase of inflammation in the alkali-burned eye. Mice with damaged eyes were either untreated or treated 24 h after the injury with an intravenous administration of fluorescent-dye-labeled MSCs that were unstimulated or pretreated with interleukin-1α (IL-1α), transforming growth factor-β (TGF-β), or interferon-γ (IFN-γ). Analysis of cell suspensions prepared from the eyes of treated mice on day 3 after the alkali burn revealed that MSCs specifically migrated to the damaged eye and that the number of labeled MSCs was more than 30-times higher in damaged eyes compared with control eyes. The study of the composition of the leukocyte populations within the damaged eyes showed that all types of tested MSCs slightly decreased the number of infiltrating lymphoid and myeloid cells, but only MSCs pretreated with IFN-γ significantly decreased the percentage of eye-infiltrating cells with a more profound effect on myeloid cells. Determining cytokine and NO production in the damaged eyes confirmed that the most effective immunomodulation was achieved with MSCs pretreated with IFN-γ, which significantly decreased the levels of the proinflammatory molecules IL-1α, IL-6, and NO. Taken together, the results show that systemically administered MSCs specifically migrate to the damaged eye and that IFN-γ-pretreated MSCs are superior in inhibiting the acute phase of inflammation, decreasing leukocyte infiltration, and attenuating the early inflammatory environment.
Insights
Systemically administered mesenchymal stromal cells (MSCs) migrate to damaged eyes. Pretreatment with interferon-gamma (IFN-γ) makes MSCs most effective at reducing acute eye inflammation and immune cell infiltration.
Area of Science:
- Ophthalmology
- Immunology
- Regenerative Medicine
Background:
- Alkali burns cause severe eye inflammation.
- Mesenchymal stromal cells (MSCs) show immunomodulatory potential.
- Systemic administration of MSCs for ocular injury is under investigation.
Purpose of the Study:
- To evaluate the efficacy of systemically administered bone-marrow-derived MSCs in mitigating acute inflammation in alkali-burned eyes.
- To determine if MSCs pretreated with specific cytokines (IL-1α, TGF-β, IFN-γ) enhance their therapeutic effect.
- To investigate MSCs' migration patterns and immunomodulatory impact on ocular inflammation.
Main Methods:
- Alkali burn model in mice.
- Intravenous injection of fluorescently labeled MSCs (unstimulated or cytokine-pretreated).
- Flow cytometry analysis of ocular immune cells and measurement of inflammatory markers (cytokines, NO) on day 3 post-injury.
Main Results:
- MSCs demonstrated specific migration to the alkali-burned eyes, with significantly higher numbers compared to control eyes.
- All tested MSC types reduced infiltrating immune cells, but IFN-γ-pretreated MSCs showed a more significant reduction, particularly in myeloid cells.
- IFN-γ-pretreated MSCs were most effective in reducing pro-inflammatory cytokines (IL-1α, IL-6) and nitric oxide (NO) levels.
Conclusions:
- Systemically administered MSCs effectively migrate to injured eyes.
- IFN-γ-pretreated MSCs exhibit superior immunomodulatory effects in acute alkali-induced ocular inflammation.
- IFN-γ-pretreated MSCs attenuate early inflammatory responses by reducing leukocyte infiltration and inflammatory mediators.
