Eyelid blood vessel and meibomian gland changes in a sclerodermatous chronic GVHD mouse model

Yang, Fan; Hayashi, Isami; Sato, Shinri; Saijo-Ban, Yumiko; Yamane, Mio; Fukui, Masaki; Shimizu, Eisuke; He, Jingliang; Shibata, Shinsuke; Mukai, Sonoyo; Asai, Kazuki; Ogawa, Mamoru; Lan, Yuqing; Zeng, Qingyan; Hirakata, Akito; Tsubota, Kazuo; Ogawa, Yoko

doi:10.1016/j.jtos.2021.10.006

Cited by 15 publications

(6 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results also showed that delgocitinib ointment had bene cial effects on in ammation and sclerotic changes in the eyelids, as well as on MGD and corneal epithelial damage. We previously reported that this sclerotic cGVHD mouse model mimics MGD and blepharitis with the depletion of MG acini, pathological brosis, and in ltration of in ammatory cells, as observed in patients with cGVHD 29,30 . MGD causes abnormalities in the lipid components of tear uid, leading to evaporative dry eye, and approximately half of the patients with ocular GVHD develop MGD 6,7 .…”

Section: Discussionmentioning

confidence: 77%

See 1 more Smart Citation

Anti-inflammatory and anti-fibrotic effects of topical pan-JAK inhibitor in a chronic graft-versus- host disease model mouse

Sato,

Asai,

Ogawa

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Systemic administration of Janus kinase (JAK) inhibitors is effective in treating chronic graft-versus-host disease (cGVHD) but is associated with side effects. Topical drug administration is an effective approach in minimizing these effects. We aimed to demonstrate the efficacy of topical delgocitinib administration in a cGVHD mouse model. Allogenic bone-marrow transplantation (BMT) was performed from B10.D2. to BALB/c mice, leading to cGVHD. cGVHD mice were treated with delgocitinib eye drops or ointments; their samples were analyzed 4 weeks post-BMT. Topical delgocitinib ointment and eye-drop administration significantly increased the meibomian-gland (MG) area and attenuated corneal epithelial damage. Pathological and immunohistochemical analyses revealed a substantial reduction in inflammation and pathological fibrosis of the skin and eyelids in delgocitinib-treated cGVHD mice. Signal transducer and activator of transcription (STAT)1, STAT3, and STAT5A phosphorylation was significantly increased in the back skin and eyelids of vehicle-treated cGVHD mice; topical delgocitinib administration significantly reduced the expression of these phosphorylated STAT molecules. Delgocitinib eye drops significantly attenuated corneal epithelial damage, MG acinar depletion, and inflammatory cells infiltration in cGVHD mouse corneas. The JAK/STAT signaling pathway was significantly upregulated in cGVHD mice. In summary, a topical delgocitinib administration attenuated cGVHD phenotype severity in the skin and eyes of cGVHD mice.

show abstract

Section: Discussionmentioning

confidence: 77%

“…After 28 days of BMT, the eyelids were collected from the right eye of each mouse. The MG area was analyzed using a topographical method, as previously reported 29,30,53 . After harvesting, photographs of the upper eyelid were taken immediately under a microscope (SZ61, Olympus, Japan) with white light.…”

Section: Eyelid Imagingmentioning

confidence: 99%

Anti-inflammatory and anti-fibrotic effects of topical pan-JAK inhibitor in a chronic graft-versus- host disease model mouse

Sato,

Asai,

Ogawa

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“… 23 The coGVHD-related inflammatory cascade induces massive meibomian gland cell apoptosis, which may cause a reduction in lipid synthesis and TG content. 43 …”

Section: Discussionmentioning

confidence: 99%

Alteration of Meibum Lipidomics Profiling in Patients With Chronic Ocular Graft-Versus-Host Disease

Zhao,

Yang,

Liao

et al. 2023

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose To investigate the characteristics of the lipid profiling in meibum of patients with chronic ocular graft-versus-host disease (coGVHD) and to detect the potential influence of anti-inflammatory therapy on these differential lipids. Methods This cross-sectional study included 25 coGVHD patients and 13 non-coGVHD after allogeneic hematopoietic stem cell transplantation. Among those with coGVHD, 14 had prior topical treatment (coGVHD (T) ), and 11 did not (coGVHD (WT) ). All participants completed ocular surface disease index questionnaire and received slit lamp examination, Schirmer's test without anesthesia, ocular surface interferometer, and meibography. Binocular meibum was collected and pooled for lipidomic analysis by liquid chromatography–mass spectrometry. Results One hundred and twenty differential lipid species were found among the three groups (96 of coGVHD (WT) vs. non-coGVHD, 78 of coGVHD (WT) vs. coGVHD (T) , and three of non-coGVHD vs. coGVHD (T) ). Compared with non-coGVHD group, coGVHD (WT) group had a significant abnormality of meibum composition, showing a significant decrease in glycerolipids, and an increase in glycerophospholipids and sphingolipids. Similar changes were also observed when coGVHD (WT) versus coGVHD (T) . CoGVHD severity was negatively associated with mono-unsaturated triglycerides (TG), (β = −214.7; 95% CI, −363.9 to −65.5; P = 0.006) and poly-unsaturated TG (β = −4019.9; 95% CI, −7758.1 to −281.6; P = 0.036). Intensity of immunosuppression was negatively associated with mono-unsaturated TG (β = −162.4; 95% CI, −268.6 to −56.2; P = 0.004) and positively associated with phosphatidylcholine (β = 332.0; 95% CI, 19.2-644.8; P = 0.038). Conclusions Altered meibum in coGVHD is characterized by a decrease of glycerolipids and an increase of glycerophospholipids and may be significantly reversed by topical anti-inflammatory therapy.

show abstract

“…In a histological study, ductal epithelial hyperkeratinization, the shedding of keratinized material into the glandular ducts leading to obstructions of the orifice, and ultimately cystic dilatation with atrophy were found in MGD ( 104 ). Moreover, ocular GVHD was characterized by ductal epithelial destruction due to lymphocyte aggregation, the sloughing of epithelial cells due to lymphocyte infiltration or pseudomembrane formation, and eventual extensive fibrosis around the orifice, ductules, ducts, and acini of the meibomian gland ( 103 , 105 – 107 ). These results suggest that ocular GVHD patients may exhibit a combination of aqueous deficiency and evaporative DED, consequently demonstrating more severe ocular discomfort and worse ocular surface conditions.…”

Section: Pathogenic Mechanism and Novel Therapeutic Targetsmentioning

confidence: 99%

Recent advances in ocular graft-versus-host disease

Cheng

Huang

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Ocular graft-versus-host-disease (GVHD) remains a significant clinical complication after allogeneic hematopoietic stem cell transplantation. Impaired visual function, pain, and other symptoms severely affect affected individuals’ quality of life. However, the diagnosis of and therapy for ocular GVHD involve a multidisciplinary approach and remain challenging for both hematologists and ophthalmologists, as there are no unified international criteria. Through an exploration of the complex pathogenesis of ocular GVHD, this review comprehensively summarizes the pathogenic mechanism, related tear biomarkers, and clinical characteristics of this disease. Novel therapies based on the mechanisms are also discussed to provide insights into the ocular GVHD treatment.

show abstract

Eyelid blood vessel and meibomian gland changes in a sclerodermatous chronic GVHD mouse model

Cited by 15 publications

References 59 publications

Anti-inflammatory and anti-fibrotic effects of topical pan-JAK inhibitor in a chronic graft-versus- host disease model mouse

Anti-inflammatory and anti-fibrotic effects of topical pan-JAK inhibitor in a chronic graft-versus- host disease model mouse

Alteration of Meibum Lipidomics Profiling in Patients With Chronic Ocular Graft-Versus-Host Disease

Recent advances in ocular graft-versus-host disease

Contact Info

Product

Resources

About