Ueno Motonobu, Lyons Bonnie L, Burzenski Lisa M, Gott Bruce, Shaffer Daniel J, Roopenian Derry C, Shultz Leonard D
Jackson Laboratory, Bar Harbor, ME 04609, USA.
Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4097-106. doi: 10.1167/iovs.05-0548.
The present study was conducted to investigate healing of alkali-burned corneas in MRL/MpJ (MRL) mice.
Gross, clinical, and histologic criteria were used to compare healing of alkali-burned corneas in MRL and control C57BL/6J (B6) mice. Effects of neutrophil depletion of B6 mice and allogeneic reconstitution of B6 mice with MRL bone marrow on wound healing were evaluated. Gene expression patterns in normal and wounded corneas were surveyed with array-based quantitative real-time RT-PCR (AQPCR).
MRL mice showed accelerated reepithelialization and decreased corneal opacity compared with B6 mice after alkali wounding. Marked inflammatory cell infiltration and fibrosis were evident in the corneas and anterior chambers of B6 mice. MRL mice showed less severe lesions, except for stromal edema. Rapid reepithelialization and reduced keratitis/iritis were also observed in neutrophil-depleted B6 mice, but not in B6 mice reconstituted with MRL bone marrow. AQPCR showed transcriptional changes of fewer genes associated with inflammation and corneal tissue homeostasis in alkali-burned corneas from MRL mice. Increased expression of an anti-inflammatory gene, Socs1, and a gene associated with healing, Mmp1a, were evident in MRL corneas.
Alkali-burned corneas heal faster and more completely in MRL mice than in B6 mice, by means of rapid reepithelialization, reduced inflammation, and reduced fibrosis. Reduced inflammation, including decreased neutrophil infiltrates and the lack of a robust proinflammatory gene expression signature correlates with the rapid healing. However, the rapid-healing phenotype is not intrinsic to MRL hematopoietic progenitor cells.
本研究旨在调查MRL/MpJ（MRL）小鼠碱烧伤角膜的愈合情况。
采用大体、临床和组织学标准比较MRL小鼠和对照C57BL/6J（B6）小鼠碱烧伤角膜的愈合情况。评估B6小鼠中性粒细胞耗竭以及用MRL骨髓对B6小鼠进行同种异体重建对伤口愈合的影响。使用基于芯片的定量实时逆转录聚合酶链反应（AQPCR）检测正常和受伤角膜中的基因表达模式。
与B6小鼠相比，MRL小鼠碱烧伤后角膜上皮再形成加速，角膜混浊减轻。B6小鼠的角膜和前房中可见明显的炎性细胞浸润和纤维化。除基质水肿外，MRL小鼠的病变较轻。在中性粒细胞耗竭的B6小鼠中也观察到角膜上皮快速再形成和角膜炎/虹膜炎减轻，但在用MRL骨髓重建的B6小鼠中未观察到。AQPCR显示，MRL小鼠碱烧伤角膜中与炎症和角膜组织稳态相关的基因转录变化较少。抗炎基因Socs1和与愈合相关的基因Mmp1a在MRL角膜中的表达增加。
MRL小鼠碱烧伤角膜的愈合速度比B6小鼠更快、更完全，这是通过快速的角膜上皮再形成、减轻炎症和减少纤维化实现的。炎症减轻，包括中性粒细胞浸润减少和缺乏强烈的促炎基因表达特征，与快速愈合相关联。然而，快速愈合表型并非MRL造血祖细胞所固有。
