Purchase this article with an account.
Stephanie Duffort, Henry Barreras, Robert Levy, Victor L Perez; Inflammatory manifestations of Ocular Graft versus Host Disease in the Cornea, Eyelid and Conjunctiva. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3055.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Graft-versus host disease (GVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) which is frequently accompanied by ocular involvement. We previously reported that in recipient mice following experimental MHC-matched minor histocompatibility-mismatched HSCT, ocular GVHD involves the presence of donor T cells in the cornea and pathologic changes in this compartment. The present study was directed to determine the kinetics of donor allo-reactive T cell presence in the cornea and investigate the presence of macrophage infiltration into the ocular adnexal tissue in recipient mice undergoing experimental allogeneic HSCT.
Experimental HSCT Model: After high-dose TBI, C3H.SW (H2b) mice were transplanted with T cell depleted bone marrow (TCD-BM) alone from B6 (H2b) EGFP transgenic mice or allo-reactive T cells from B6 (H2b) CD45.1 transgenic mice. Recipients were monitored weekly for signs of systemic and oGVHD. In vivo fluorescent intravital microscopy was performed to track EGFP-labeled TCD-BM cells. Cornea, lids and conjunctiva were harvested weekly beginning 2 weeks post-HSCT for evaluation by histology, immunohistochemistry (IHC) and flow-cytometry.
Mice transplanted with donor TCD-BM+T cells underwent weight loss and began exhibiting clinical signs of systemic GVHD. EGFP-labeled TCD-BM cells were detectable in the lid margin, conjunctiva and cornea of animals undergoing systemic GVHD by week two after transplantation and showed massive increased fluorescence by week six. Allo-reactive T cells were also present at week two which peaked at week four. IHC confirmed the presence of T cells and macrophage infiltration in the lid margin and conjunctiva. By week six, lid pathology showed significantly elevated donor inflammatory cell infiltrate consisting primarily of macrophages and T cells compared to control (TCD-BM only) recipients.
GVHD is a complex systemic disorder involving multiple tissues including the eye. The present study demonstrated that following HSCT, allo-reactive T cells appear first in the lid margin, conjunctiva and cornea and subsequently the recruitment of macrophages in the ocular adnexa can be identified followed by tissue damage.
This PDF is available to Subscribers Only