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Role of Extracellular Lumican in Corneal Stromal Infection

Hayashi, Yasuhito MD, PhD; Ohashi, Yuichi MD, PhD

doi: 10.1097/ICO.0b013e3181ae9a68

Purpose: To explore the role of lumican in polymorphonuclear neutrophil granulocyte (PMN) migration in corneal stroma after bacterial infection.

Methods: Lumican wild-type (Lum+/ +) green fluorescent protein (GFP)-positive PMNs were transplanted into lumican knockout (Lum−/ ) and heterozygous control (Lum+/ ) mice followed by corneal stromal injection of Staphylococcus aureus conjugated with pH-sensitive dye that expresses fluorescein when trapped in lysosomes.

Results: In Lum+/ corneal stroma, many small triangular or spindle-shaped cells labeled by pH-sensitive dye appeared within 10 minutes after S. aureus injection, whereas in Lum−/ corneal stroma, large cells or large cell complexes (morphologically, macrophages and macrophage-derived lymphatic vessels) appeared. Transplanted GFP-positive PMNs appeared in Lum+/ corneal stroma within 1 hour after S. aureus injection and were concentrated in the central injection area at 2 hours after injection. In Lum−/ , on the other hand, relatively few GFP-positive cells were observed in corneal stroma even ≤ 24 hours after injection of bacteria.

Conclusions: Extracellular lumican is required for PMN migration in corneal stroma. In lumican null mouse cornea, macrophages and macrophage-derived lymphatic vessels act as first defense against staphylococcal infection.

From the *Department of Ophthalmology; and †Regenerative Medicine, Ehime University School of Medicine, Ehime, Japan.

Supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology (No. 19592024).

Reprints: Yasuhito Hayashi, MD, PhD, Department of Ophthalmology, Ehime University School of Medicine, 454 Shitsukawa, Toon, Ehime 791-0295, Japan (e-mail:

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