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H.-Y. Zhu, R. W. Beuerman, M. Stern; Mouse Model of Postsurgical Intraocular Inflammation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1157.
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Postsurgical intraocular inflammation can be a consequence of surgery or trauma. The purpose of this study was to establish an in vivo mouse model of intraocular inflammation following surgery in the normal eye, and to examine key molecules in the regulation of the inflammatory response.
Surgery was performed on one eye of C57/BL6 mice and the other eye was control. A scleral incision was created approximately 0.4mm from limbus with a sapphire blade. The blade was manipulated subscleraly, penetrated iris root and was introduced into the anterior chamber. The incision was closed by 10-0 nylon sutures. In vivo confocal imaging was performed in a preplanned fashion to analyze cell infiltration in the cornea, anterior chamber and iris at PO days1, 3, 5 and 7. Tissues were collected on the same schedule. The expression of S100A8, S100A9 and high-mobility-group B (HMGB) 1 was examined by immunofluorescent staining and confirmed by quantitative real-time polymerase chain reaction (RT-PCR).
Using confocal microscopy, cell infiltration was not observed in the anterior chamber in normal eyes (n=10), but was seen after surgery (n=10) at day1 (66±5cells), peaking at day3 (316±52cells), and decreasing over time to day7 (3±1cells). RT-PCR showed S100A8/9 mRNA levels in iris were up-regulated (p<0.05) after surgery at day1, peaking at day3, and remaining elevated to day7. mRNA levels of S100A8/9 in the cornea, HMGB1 in the cornea and iris increased (p<0.05) at PO day1 and decreased over time. Immunofluorescent staining of S100A8/9 and HMGB1 corroborated the RT-PCR results. HMGB1 and S100A8/9 were not detectable in unwounded iris, but were upregulated after surgery, peaking in the cornea stroma at day1 and in the iris at day3, and decreasing over time. Staining of S100A8/9 and HMGB1 in the cornea epithelium was present at low levels and did not appear to increase after surgery.
The mouse model provides a simple tool for the dissection of molecules involved in intraocular inflammation and the evaluation of drug delivery strategies in treating intraocular inflammation.
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