Accelerated wound healing of alkali-burned corneas in MRL mice is associated with a reduced inflammatory signature.

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Bone-Marrow-Transplantation, Burns-Chemical, Carrier-Proteins, Collagenases, Comparative-Study, Corneal-Diseases, Disease-Models-Animal, Epithelium-Corneal, Eye-Burns, Flow-Cytometry, Gene-Expression-Regulation, Male, Matrix-Metalloproteinases, Mice-Inbred-C57BL, Mice-Inbred-MRL-lpr, Neutrophils, Oligonucleotide-Array-Sequence-Analysis, RNA-Messenger, Repressor-Proteins, Research-Support-N, I, H, -Extramural, Reverse-Transcriptase-Polymerase-Chain-Reaction, Sodium-Hydroxide, Suppressor-of-Cytokine-Signaling-Proteins, Wound-Healing

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Invest Ophthalmol Vis Sci 2005 Nov; 46(11):4097-106


PURPOSE: The present study was conducted to investigate healing of alkali-burned corneas in MRL/MpJ (MRL) mice. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.