Observation of Chronic Graft-Versus-Host Disease Mouse Model Cornea with In Vivo Confocal Microscopy.
Shota ShimizuShinri SatoHiroko TaniguchiEisuke ShimizuJingliang HeShunsuke HayashiKazuno NegishiYoko OgawaShigeto ShimmuraPublished in: Diagnostics (Basel, Switzerland) (2021)
Graft-versus-host disease (GVHD) is a major complication after hematopoietic stem cell transplantation (HSCT), and ocular GVHD can cause severe dry eye disease that can lead to visual impairment. Epithelial damage, vascular invasion, corneal fibrosis, and corneal perforation may occur in severe cases. It is generally accepted that inflammatory cells such as dendritic cells and T cells contribute to this pathological condition. However, it is still unknown what pathological condition occurs on the ocular surface after HSCT, and when. We therefore observed the dynamics of inflammatory cells in the cornea of chronic GVHD (cGVHD) model mice from 1 to 4 weeks after bone marrow transplantation (BMT) by in vivo confocal microscopy (IVCM) and considered the relationship with the pathophysiology of ocular GVHD (tear volume, corneal epithelial damage). In the allogeneic group, neovascularization occurred in all eyes at 1 week after BMT, although almost all vessels disappeared at 2 weeks after BMT. In addition, we revealed that infiltration of globular cells, and tortuosity and branching of nerves in the cornea occurred in both cGVHD mice and human cGVHD patients. Thus, we consider that cGVHD mouse model study by IVCM reproduces the state of ocular GVHD and may contribute to elucidating the pathological mechanism for ocular GVHD.
Keyphrases
- induced apoptosis
- mouse model
- allogeneic hematopoietic stem cell transplantation
- bone marrow
- oxidative stress
- dendritic cells
- cell cycle arrest
- optical coherence tomography
- endothelial cells
- mesenchymal stem cells
- acute myeloid leukemia
- endoplasmic reticulum stress
- immune response
- early onset
- ejection fraction
- single cell
- stem cells
- randomized controlled trial
- cell death
- acute lymphoblastic leukemia
- stem cell transplantation
- diabetic retinopathy
- cell proliferation
- skeletal muscle
- wound healing
- chronic kidney disease
- gestational age
- induced pluripotent stem cells
- wild type