Meibomian Gland Dysfunction in Ocular Graft vs. Host Disease: A Need for Pre-Clinical Models and Deeper Insights
Abstract
:1. Introduction
2. Overview of Meibomian Gland Biology
3. Secretory and Postulated Regeneration Properties of the Meibomian Gland
4. Pre-aHSCT Conditioning Regimen Can Affect Normal Meibomian Gland Health
5. Evidence of Inflammatory Immune Response in oGvHD and the Meibomian Gland
6. Pre-Clinical Models of oGvHD and the Meibomian Gland
7. Discussion
8. Conclusions
9. Literature Search Strategy
Author Contributions
Funding
Conflicts of Interest
Abbreviations
aHSTC | Allogeneic hematopoietic stem cell transplantation |
CD | Cluster of Differentiation |
GvHD | Graft-vs-host disease |
HLA | Human leukocyte antigen |
MHC | Major histocompatibility complex |
MiHA | Minor histocompatibility antigen |
MDA | Malondialdehyde |
MGD | Meibomian glad dysfunction |
oGvHD | Ocular graft-vs-host-disease |
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Study | Purpose | Model Description | Pre-Conditioning Regimen | Main Ocular Findings | Therapy/OutCome | |||
---|---|---|---|---|---|---|---|---|
Cornea | Conjunctiva | Lacrimal Gland | Meibomian Gland | |||||
[22] | To develop a novel topical antifibrotic treatment against ocular chronic GVHD using vitamin A-coupled liposomes containing short interfering RNA against heat shock protein 47 (VA-lip HSP47) eye drops. | Minor histocompatibility-antigen mismatched mouse model Donor: B10.D2 (H-2d) recipient: BALB/c (H-2d) | Total body irradiation | No information | No information | Infiltration of HSP47+ fibroblasts Increased fibrosis Increased collagen deposition | No information | Instillation of VA-lip HSP47 agent reduced fibrosis, collagen deposition and restored normal levels of tear production |
[18] | To investigate the role of ocular surface glycocalyx and mucins in graft versus host disease (GVHD)-associated dry eye and ameliorative effect of topical rebamipide, a mucin secretagogue, on GVHD-associated dry eye | Major histocompatibility class I mismatch Donor: C57BL/6 Ly 5.2+ Recipients: B6D2F1 (F1) | Total body irradiation | Presence of dry eye phenotype with keratopathy indicated by significant punctate and plaque corneal staining Reduced glycocalyx density and thickness Reduced Muc 1 and M4 and increased Muc 16 | Decrease in palpebral conjunctiva goblet cells | Reduced tear film volume with concomitant reduction in Muc5ac | No information | Instillation of 2% rebamipide in balance salt solution vehicle twice daily (left eye only) attenuated reduction in tear production and corneal damage |
[45] | To evaluate the efficacy of entospletinib (ENTO), tyrosine kinase SYK inhibitor on the clinical (clinical and skin) aspects of GVHD | Donor: C57BL/6 (H2b) Recipient: BALB/c (H2kd) Clarification on matching status need | Total body irradiation | No specific information | Chemosis, redness | No specific information | Eyelid edema and blepharitis but no direct mention of the meibomian glands | ENTO administration resulted in profound improvements in clinical eye as well as other systemic GvHD scores. |
[21] | To develop a novel clinical scoring criterion for identifying degrees of ocular pathology at both the ocular surface and adnexa in oGvHD | MHC-matched, minor transplantation antigen–mismatched allogeneic model of matched unrelated donor Donors: B6 mice (H-2b, Thy1.1)//(eGFP) B6 transgenic (H2b) Recipients: C3H.SW (H2b) | Total body irradiation | Corneal ulceration, epithelial haze, corneo-limbal eGFP+ immune cell infiltrates | No information | No specific information | Eye lid oedema and closure with eGFP+ immune cell infiltrates but no specific mention of the meibomian gland | No information |
[42] | To identify the kinetics and origin of ocular infiltrating T cells in a preclinical model of graft-versus-host disease (GVHD) that induces eye tissue damage. | Major histocompatibility complex-matched, minor histocompatibility-mismatched hematopoietic stem cell transplant mouse model. Donor: C56BL/6 mice (H2b, Ly9.1−) Recipient: C3H.SW, H2b, Ly9.1+ | Total body irradiation | Epitheliopathy with increased staining 3–4wks post-transplant Infiltration of CD4+ and CD8+ T cells, macrophages, monocytes and neutrophils Upregulation of IFNy, TNFα and IL-6 genes | Reduced goblet cells density Apparent atrophy of fornix | Infiltration of T cells and macrophages | No information | No information |
[20] | To establishes a model of GVHD with cornea and limbus involvement | Major/sex mismatch and Donor: Male C57BL/6 (H2b) Recipient: Female BALB/c (H2k) | Total body irradiation | Atrophic epitheliopathy with vacuolization Stromal oedema, neovascularization, and inflammatory/lymphocytic infiltrates Limbus show epithelial satellitosis | Focal epithelial loss, lymphocytic exocytosis, necrosis Mononuclear cells and microvesicular infiltrates | Apparent ductal fibrosis Ductal/Interlobu-lar infiltration with eosinophils | Crusted/erythe-matosus eyelids but no direct mention of the meibomian gland | No information |
[19] | To describe lacrimal gland involvement in graft versus-host disease | Major histocompatibility class I mismatch Donors: C57BL/6 Ly 5.2+ (Allogeneic), B6D2F1 (F1) (Syngeneic) Recipients: B6D2F1 (F1) | Total body irradiation | No information | No information | Periductal inflammation fibrosis, apoptosis, accumulation of ductal debris and stasis of ducts Infiltration of of CD3+, CD8+ and CD4+ positive T cells Overall higher disease scores in the allogeneic group | Lid inflammation but no direct mention of the meibomian gland involvement | No information |
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Appenteng Osae, E.; Steven, P. Meibomian Gland Dysfunction in Ocular Graft vs. Host Disease: A Need for Pre-Clinical Models and Deeper Insights. Int. J. Mol. Sci. 2021, 22, 3516. https://doi.org/10.3390/ijms22073516
Appenteng Osae E, Steven P. Meibomian Gland Dysfunction in Ocular Graft vs. Host Disease: A Need for Pre-Clinical Models and Deeper Insights. International Journal of Molecular Sciences. 2021; 22(7):3516. https://doi.org/10.3390/ijms22073516
Chicago/Turabian StyleAppenteng Osae, Eugene, and Philipp Steven. 2021. "Meibomian Gland Dysfunction in Ocular Graft vs. Host Disease: A Need for Pre-Clinical Models and Deeper Insights" International Journal of Molecular Sciences 22, no. 7: 3516. https://doi.org/10.3390/ijms22073516