학술논문

Novel Scoring Criteria for the Evaluation of Ocular Graft-versus-Host Disease in a Preclinical Allogeneic Hematopoietic Stem Cell Transplantation Animal Model
Document Type
article
Source
Transplantation and Cellular Therapy. 22(10)
Subject
Immunology
Biomedical and Clinical Sciences
Cardiovascular Medicine and Haematology
Ophthalmology and Optometry
Stem Cell Research
Eye Disease and Disorders of Vision
Rare Diseases
Hematology
Regenerative Medicine
Transplantation
2.1 Biological and endogenous factors
Aetiology
Inflammatory and immune system
Animals
Conjunctivitis
Dry Eye Syndromes
Eye Diseases
Eyelid Diseases
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Inflammation
Mice
Models
Animal
Severity of Illness Index
Transplantation
Homologous
Unrelated Donors
Allogeneic hematopoietic stem cell transplantation
Graft-versus-host disease
Lacrimal gland
Ocular GVHT
Ocular adenexa
Ocular scoring
Clinical Sciences
Cardiovascular medicine and haematology
Language
Abstract
Ocular complications occur after transplantation in 60% to 90% of chronic graft-versus-host disease (GVHD) patients and significantly impair vision-related quality of life. Ocular surface inflammation and dry eye disease are the most common manifestations of ocular GVHD. Ocular GVHD can be viewed as an excellent preclinical model that can be studied to understand the immune pathogenesis of this common and debilitating disease. A limitation of this is that only a few experimental models mimic the ocular complications after hematopoietic stem cell transplantation (HSCT) and have focused on the acute GVHD process. To address this issue, we used a preclinical animal model developed by our group where ocular involvement was preceded by systemic GVHD to gain insight regarding the contributing immune mechanisms. Employing this "matched unrelated donor" model enabled the development of clinical scoring criteria, which readily identified different degrees of ocular pathology at both the ocular surface and adnexa, dependent on the level of conditioning before HSCT. As far as we are aware, we report for the first time that these clinical and immune responses occur not only on the ocular surface, but they also heavily involve the lid margin region. In total, the present study reports a preclinical scoring model that can be applied to animal models as investigators look to further explore GVHD's immunologic effects at the level of the ocular surface and eyelid adnexa compartments. We speculate that future studies will use this clinical scoring index in combination with what is recognized histologically and correlated with serum biomarkers identified in chronic/ocular GVHD.