Aims/background-There are more reagents and information available for
immunological studies in the mouse compared with other animals. Unfort
unately, the mouse penetrating keratoplasty model is associated with h
igh background inflammation which hinders study of the immune response
to the graft. To mitigate this drawback, a murine orthotopic corneal
interlamellar transplantation model with mild non-specific inflammatio
n was developed. Methods-A 1.5 mm diameter full thickness donor cornea
l button was placed in a 2 mm diameter recipient corneal interlamellar
pocket without placement of a suture. The clinical course of graft st
atus was studied daily for 60 days in 30 allografts (donor strain CBA
101 (H-2(k)) to recipient NM (H-2(q))) and 30 syngeneic grafts (NM to
NIH) by slit lamp biomicroscopy and scored for neovascularisation, opa
city, oedema, and granularity. In another cohort of animals, histologi
cal observation was performed after 30 minutes and on days 10, 20, 30,
and 40 after transplantation (four allografts and four syngeneic graf
ts per time point). Histological study was also performed on grafts wi
thout donor epithelium and on interlamellar pockets without grafts. Re
sults-There was significantly more neovascularisation (NV), opacity, o
edema, and granularity in 24/30 allografts (80%) than in syngeneic gra
fts. Such grafts were defined as rejected. The median time to rejectio
n was 21 days (range 18 to >60 days). By histology, some allografts sh
owed moderate to heavy cell infiltration which correlated with clinica
l scores of NV (4-5), opacity (1-3), oedema (1-3), and granularity (1-
3). Such infiltration was absent in other allografts and syngeneic gra
fts. Conclusion-Surgically, corneal interlamellar transplantation coul
d be accomplished in the mouse and rejection could be clearly defined.
The model can therefore be useful for in situ study of cell and molec
ular aspects of corneal graft rejection.