Effects of Mesenchymal Stem/Stromal Cells in T cell-mediated Dry Eye Model in Mice

Abstract

 

Purpose

 

To investigate the effects of mesenchymal stem/stromal cells (MSCs) in T cell-mediated dry eye model in mice that was induced by concanavalin A (ConA) into lacrimal glands.

 

Methods

 

Either phosphate buffered saline (PBS) or Con A (10mg/ml) was injected into lacrimal glands in mice. Immediately after ConA injection, balanced salt solution (BSS), 1X10³ MSCs, or 1X10⁵ MSCs were injected periorbitally near lacrimal glands. One week later, tear production was measured by phenol red thread test, and levels of interleukin (IL) -2 and interferon (IFN)-γ were evaluated in the lacrimal glands and the ocular surface using real time RT-PCR. Infiltration of inflammatory cells and damage to the lacrimal glands were evaluated by histopathology, and ocular surface goblet cell count was performed. Also, infiltration of immune cells in lacrimal glands was analyzed by immunohistochemistry and flow cytometry.

 

Results

 

Con A injection induced T cell-mediated dry eye in mice by causing T cell infiltration, increasing pro-inflammatory cytokine expression. Also tear production was significantly decreased (p = 0.0006) and goblet cell count was reduced (p = 0.02). A Both 1X10³ MSCs and 1X10⁵ MSCs significantly improved tear production (vs. ConA+BSS group, p=0.001 and p=0.0006, respectively). Also, MSCs significantly decreased the levels of IL-2 and IFN-γ in the ocular surface and lacrimal glands. Similarly, the numbers of IFN-γ-expressing CD4+ cells in lacrimal glands were significantly lower in MSC-treated groups compared to Con A+BSS group (p = 0.008 for 1X10³ MSCs, p = 0.004 for 1X10⁵ MSCs).

 

Conclusions

 

Periorbital injection of MSCs reduce inflammation of the ocular surface and lacrimal glands, and improve tear production in Con A-induced dry eye model in mice.

 

 

Tear production was significantly reduced after ConA injection, but both 1X10³ MSCs and 1X10⁵ MSCs significantly improved tear production. *** p<0.005

 

 

The expression of IL-2 and IFN-r in the lacrimal glands were significantly increased after ConA injection, but reduced with MSCs injection. *p<0.05, **p<0.01

 

Keywords: 486 cornea: tears/tear film/dry eye • 721 stem cells