Lau C H, Nicholls S M, Easty D L
Division of Ophthalmology, Medical School, University of Bristol.
Br J Ophthalmol. 1998 Mar;82(3):294-9. doi: 10.1136/bjo.82.3.294.
AIMS/BACKGROUND: There are more reagents and information available for immunological studies in the mouse compared with other animals. Unfortunately, the mouse penetrating keratoplasty model is associated with high background inflammation which hinders study of the immune response to the graft. To mitigate this drawback, a murine orthotopic corneal interlamellar transplantation model with mild non-specific inflammation was developed.
A 1.5 mm diameter full thickness donor corneal button was placed in a 2 mm diameter recipient corneal interlamellar pocket without placement of a suture. The clinical course of graft status was studied daily for 60 days in 30 allografts (donor strain CBA 101 (H-2k) to recipient NIH (H-2q) and 30 syngeneic grafts (NIH to NIH) by slit lamp biomicroscopy and scored for neovascularisation, opacity, oedema, and granularity. In another cohort of animals, histological observation was performed after 30 minutes and on days 10, 20, 30, and 40 after transplantation (four allografts and four syngeneic grafts per time point). Histological study was also performed on grafts without donor epithelium and on interlamellar pockets without grafts.
There was significantly more neovascularisation (NV), opacity, oedema, and granularity in 24/30 allografts (80%) than in syngeneic grafts. Such grafts were defined as rejected. The median time to rejection was 21 days (range 18 to > 60 days). By histology, some allografts showed moderate to heavy cell infiltration which correlated with clinical scores of NV (4-5), opacity (1-3), oedema (1-3), and granularity (1-3). Such infiltration was absent in other allografts and syngeneic grafts.
Surgically, corneal interlamellar transplantation could be accomplished in the mouse and rejection could be clearly defined. The model can therefore be useful for in situ study of cell and molecular aspects of corneal graft rejection.
目的/背景：与其他动物相比，小鼠有更多的试剂和信息可用于免疫学研究。不幸的是，小鼠穿透性角膜移植模型伴有严重的背景炎症，这阻碍了对移植物免疫反应的研究。为了减轻这一缺点，开发了一种具有轻度非特异性炎症的小鼠原位角膜层间移植模型。
将直径1.5毫米的全层供体角膜纽扣置于直径2毫米的受体角膜层间袋中，不进行缝合。通过裂隙灯显微镜对30只同种异体移植（供体品系CBA 101（H-2k）至受体NIH（H-2q））和30只同基因移植（NIH至NIH）的移植物状态临床过程进行每日研究，为期60天，并对新生血管形成、混浊、水肿和颗粒度进行评分。在另一组动物中，在移植后30分钟以及第10、20、30和40天进行组织学观察（每个时间点4只同种异体移植和4只同基因移植）。还对没有供体上皮的移植物和没有移植物的层间袋进行了组织学研究。
24/30只同种异体移植（80%）中的新生血管形成（NV）、混浊、水肿和颗粒度明显多于同基因移植。此类移植物被定义为被排斥。排斥的中位时间为21天（范围18至>60天）。通过组织学检查，一些同种异体移植显示中度至重度细胞浸润，这与NV（4-5）、混浊（1-3）、水肿（1-3）和颗粒度（1-3）的临床评分相关。其他同种异体移植和同基因移植中没有这种浸润。
在手术方面，小鼠角膜层间移植可以完成，并且排斥反应可以明确界定。因此，该模型可用于角膜移植排斥反应的细胞和分子方面的原位研究。
