Cellular events in the normal and inflamed cornea.
OBJECTIVE
Although normal cornea is an avascular transparent structure, bone marrow (BM)-derived cells exist in situ even in noninflamed conditions. We evaluated constitutive cellular trafficking into the cornea in the naive state and investigated how corneal inflammation may be initiated by various stimuli.


METHODS
BM chimeric mice were generated using BM from enhanced green fluorescent protein (eGFP) transgenic mice. Corneas of chimeric mice were carefully studied by fluorescent biomicroscopy until 6 months after transplantation. To analyze initiation of cellular events in corneal immune response, we cauterized the center of the cornea or inoculated IL-1 beta into the corneal micropocket. Cellular events were analyzed by flow cytometry.


RESULTS
At 2 weeks after BM transplantation, GFP cells gradually migrated into the cornea from the limbal area and were distributed over the entire cornea at 6 months. In both the cauterization and micropocket assays, infiltration of neutrophils and macrophages occurred on days 2 and 4, respectively. Depletion of neutrophils by anti-Gr-1 Ab significantly reduced corneal edema/opacity induced by cauterization. IL-1 beta-induced angiogenesis was markedly reduced in monocyte chemoattractant protein-1 knockout mice.


CONCLUSIONS
BM-derived cells are recruited into the normal cornea and may be essential to maintain corneal clarity. In the inflamed cornea, neutrophils might be responsible for acute corneal edema/opacity and macrophages for corneal angiogenesis and chronic inflammation.
Sonoda
Koh-Hei
KH
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. sonodak@med.kyushu-u.ac.jp
Nakao
Shintaro
S
Nakamura
Takahiro
T
Oshima
Toru
T
Qiao
Hong
H
Hisatomi
Toshio
T
Kinoshita
Shigeru
S
Ishibashi
Tatsuro
T
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002425:Cautery; D019070:Cell Lineage; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000172:deficiency; D002678:Chimera; D016510:Corneal Neovascularization / Q000139:chemically induced; D004343:Drug Implants; D005260:Female; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000008:administration & dosage; D007634:Keratitis / Q000209:etiology / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009504:Neutrophils
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004343:Drug Implants; D007375:Interleukin-1