Ocular graft vs host disease mouse model
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Ocular graft versus host disease (OGvHD) develops in nearly 50% of patients after allogeneic hematopoietic stem cell transplantation (HSCT) and frequently manifests as dry eye disease (DED).  The aim of this study was to evaluate the efficacy of a single subconjunctival (SCJ) dose of adeno-associated virus (AAV) gene therapy encoding human leukocyte antigen G (HLA-G) isoforms 1 and 5 to induce ocular immune tolerance and inhibit development of clinical signs of OGvHD.,  A Major histocompatibility mismatch chronic OGvHD murine model was evaluated. Seven days after HSCT, mice were dosed subconjunctivally with scAAV8-HLA-G1/5 (1e9vg/eye), topical cyclosporine (CSA) (twice daily), or left untreated.  Body weights and tear production (red thread test) were recorded, and eyelid, corneal opacity, and corneal fluorescein retention were scored through day 44 after HSCT.
Body weights were recorded prior to ocular injections and every other day thereafter. Tear production was recorded weekly by using phenol red threads (PRT) (Zone Quick Tread, Oasis Medical, San Dimas, CA, USA) placed into the lateral canthus of the eye for 20 s, and the amount of tear fluid was recorded in mm. Â Clinical scores (0-4) of eyelid inflammation, corneal opacity, and corneal fluorescein retention were recorded, following slit lamp biomicroscopy (KOWA SL-17, Torrance, CA), three times per week through day 44 after HSCT with the observer masked to the treatment groups.
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眼移植物抗宿主病(Ocular graft versus host disease, OGvHD)在异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation, HSCT)后近50%的患者中发生,且常表现为干眼病(dry eye disease, DED)。本研究旨在评估单次结膜下(subconjunctival, SCJ)给药的编码人类白细胞抗原G(human leukocyte antigen G, HLA-G)1型和5型亚型的腺相关病毒(adeno-associated virus, AAV)基因疗法,诱导眼部免疫耐受并抑制OGvHD临床症状发展的疗效。
本研究评估了主要组织相容性不相合慢性OGvHD小鼠模型。在HSCT后7天,小鼠分别接受结膜下给药scAAV8-HLA-G1/5(1×10^9vg/眼)、局部环孢素A(cyclosporine, CSA)(每日两次)或不进行任何处理。记录小鼠体重与泪液产生量(棉线试验),并在HSCT后第44天前对眼睑、角膜混浊及角膜荧光素钠潴留情况进行评分。
体重在眼部给药前及之后每隔一日记录一次。泪液产生量采用酚红棉线试验(phenol red threads, PRT)(Zone Quick Tread, Oasis Medical, 美国加利福尼亚州圣迪马斯市)每周检测一次:将棉线置于眼外眦20秒,以毫米为单位记录泪液浸湿长度。
采用裂隙灯生物显微镜(KOWA SL-17, 美国加利福尼亚州托伦斯市)进行检测,由对治疗分组不知情的观察者每周三次在HSCT后第44天前记录眼睑炎症、角膜混浊及角膜荧光素钠潴留的临床评分(0~4分)。
最为突出的……,相关数据存储于Microsoft Excel数据库。
创建时间:
2025-07-16



