Overexpression of IL-8 in the cornea induces ulcer formation in the SCID mouse

• Published in: British journal of ophthalmology 2006-05, Vol.90 (5), p.612-615
• Main Authors: Oka, M, Norose, K, Matsushima, K, Nishigori, C, Herlyn, M
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenovirus; adenovirus vector; Adenoviruses; Angiogenesis; Animals; Biological and medical sciences; Cornea; Cornea - metabolism; Cornea - pathology; Corneal Ulcer - etiology; Corneal Ulcer - pathology; Cytotoxicity; Genetic Vectors - administration & dosage; IL-8; Immunohistochemistry; Infections; interleukin; Interleukin-8 - genetics; Interleukin-8 - metabolism; Laboratory Science - Scientific Report; Medical sciences; Mice; Mice, SCID; Miscellaneous; mouse model; Neutrophils; Ophthalmic Solutions; Ophthalmology; Pathogenesis; PFU; plaque forming units; Proteins; Rodents; SCID; severe combined immunodeficiency; Transduction, Genetic - methods; ulcer; Ulcers
• ISSN: 0007-1161; 1468-2079
• DOI: 10.1136/bjo.2005.084525

Aims: Although interleukin 8 (IL-8) is not produced in the normal cornea, it has been detected there in several pathological conditions. In this study, the direct effects of IL-8 overexpression on the cornea was examined. Methods: The corneal surface of severe combined immunodeficiency mice was infected by the adenovirus vector encoding human IL-8 (IL-8/Ad5) and clinical and pathological changes were observed at various time points. Results: Clinically, marked angiogenesis and ulcer formation in the cornea were observed by 12 hours and 24 hours, respectively. Histologically, prominent angiogenesis was observed in the corneal stroma at 12 hours. Cleft formation between the corneal epithelium and stroma, and neutrophil infiltration into the corneal stroma were seen at 16 hours. By 24 hours after the infection with IL-8/Ad5, a shallow ulcer was formed in the cornea. In contrast, infection with the control adenovirus carrying the β galactosidase gene (LacZ) showed neither corneal ulceration nor neutrophil infiltration. Immunohistochemical analysis showed that infection with IL-8/Ad5 resulted in the production of IL-8 by corneal and conjunctival stromal cells. Conclusion: Our results indicate that IL-8 overexpression in corneal tissue causes ulcer formation in the cornea through chemoattraction of neutrophils, suggesting the aetiological role of IL-8 in some types of corneal ulcers.