Murine model of ocular graft versus host disease

Abstract

Abstract: : Purpose: To describe a murine model of ocular graft vs. host disease (GVHD). Methods: MHC matched transplantation (which mimics HLA matched transplantation) was performed. AKR/J mice (MHC H–2k) received lethal irradiation (9gray) followed by transplantation with 1x10⁷ BM cells without (control) or with 2 or 4x10⁶ splenic lymphocytes from B10.BR donors (MHC H–2k). Controls consisted of 1) untreated AKR/J mice, 2) irradiated but not transplanted mice, and 3) mice transplanted with marrow alone, which should not develop GVHD. Clinically, mice eyes were evaluated before and after the transplant with external exam, Schirmers, and flourescein staining tests. At the time of death or when scarified due to morbidity (typically day 14–35), the lacrimal glands (harderian glands), lids, and the conjunctiva were examined histolopathologically. These animals were also evaluated for systemic GVHD. Results: Mice with GVHD showed clinical features of erythematous lids, increased fluorescein staining on the ocular surface, and decrease in Schirmers. Of the 12 animals with systemic GVHD histopathologically (in the gut, liver, and skin), 10 animals showed findings consistent with ocular GVHD with apoptosis of the lacrimal/harderian glands, meibomian glands, and in the epithelial layer of the conjunctiva. Of the 10 animals positive for ocular GVHD, skin GVHD was always present, but 2 animals were without gut GVHD and 5 animals were without liver involvement. There was also variable degree of organ involvement, which mirrors human systemic and ocular GVHD. Conclusions: A murine model of ocular graft vs. host disease is described. To our knowledge, it is the first murine model of ocular GVHD. Further studies to better characterize this model are ongoing.

Keywords: transplantation • cornea: tears/tear film/dry eye • uveitis–clinical/animal model