Abstract
Purpose :
Acute ocular Graft-versus-Host disease (GVHD) is a highly prevalent disorder occurring in allogeneic hematopoietic stem cell transplantation (HSCT), and donor lymphocyte infusion and represents an unmet medical need. The purpose of this study was to describe and quantify for the first time the course of acute ocular GVHD in an established model of systemic MHC mismatched GVHD.
Methods :
GVHD was induced by preconditioning BALB/c mice with myeloablative total body irradiation, and then transplanting T depleted bone marrow cells (BM), repleted with mature splenocytes (BM+T). Mice transplanted with BM only were used as controls. Acute ocular GVHD was assessed by quantifying: epithelial corneal damage, tear secretion as well as overall systemic GVHD (scored based on: activity, hunch, fur, skin and weight) 3 times per week for 28 days post-transplantation. Furthermore, we quantified eyelid fur loss as a measure of lid disease.
Results :
Both early acute (0-15 days) and late acute (16-28 days) ocular GVHD induced corneal epithelial damage (BM vs BM+T Day 15 +20.76%, P=0.0003; Day 28 +10.66%, P=0.0129). Systemic GVHD scores showed differences starting from one-week post-transplantation (Day 7 BM=2.66 vs BM+T=4.2, P=0.0115; Day 28 BM=0.66 vs BM+T=9, P<0.0001). Tear secretion was significantly increased in the BM+T group in the early acute phase (Day 11 BM=0.92 vs BM+T=2.33, P=0.0081) while it significantly decreased in the late acute phase (Day 27 BM=2.33 vs BM+T=0.92, P = 0.0180). Moreover, eyelid inflammation was significantly higher in BM+T as opposed to BM animals in the early acute phase (Day 1 BM=0 vs BM+T=1.5, P< 0.0001; Day 4 BM=0 vs BM+T=2, P=0.0007; and Day 6 BM=0 vs BM+T=2.1, P=0.0003).
Conclusions :
Our findings indicate that acute GVHD has a deep impact on ocular surface health. We hypothesize that intervention in such an early stage might be beneficial for the prevention of chronic disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.