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M. Stepp, S.P. Ghosh, Y. Liu, R.A. Jurjus, H.L. Chandler, C.M. H. Colitz, D.F. Kusewitt; Resolution of Spontaneous Epithelial Erosions After Corneal Debridement Wounding in Mice Is Not Altered by Treatment of Mice With Oral Doxycycline . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2758.
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When 8 wk old Balb/c mice are subjected to large (2.5 mm) manual debridement wounds on their corneas, the wounds close initially but then recurrent epithelial erosions occur spontaneously several weeks later with high frequency and a partial corneal epithelial stem cell deficiency develops. These studies were conducted to determine whether oral treatment of mice with low doses of doxycycline might reduce the erosion frequency and improve healing in mice.
2.5 mm wounds were made to the eyes of 8 wk old Balb/c mice. After wounding, mice were separated into 3 treatment groups. 10 were given water alone, 10 were given water supplemented with 200 mg/L dox from the time of wounding, and 8 were given water supplemented with 200 mg/L dox beginning 2 wk after wounding. Eyes were evaluated for evidence of erosions at 1, 2, 4, and 6 wk after wounding. After 6 wk, all mice were sacrificed, a suture was placed in the temporal sclera of each eye, the left and right eyes were separated, and eyes were processed for whole mount immunofluorescence microscopy.
At 1, 2, 4, and 6 wk after wounding, 40%, 80%, 80%, and 25% of the eyes of mice on water alone showed evidence of open wounds. For mice supplemented with dox at the time of wounding, 15%, 65%, 95%, and 35% of the eyes showed evidence of erosions at 1, 2, 4, and 6 wk. For mice supplemented with dox beginning 2 wk after wounding, 63%, 75%, 63%, and 25% of the eyes showed evidence of erosions at 1, 2, 4, and 6 wk.
Balb/c mice develop spontaneous erosions after 2.5 mm wounds with the erosion frequency highest between 2 and 4 wk after wounding. While adding dox to the water the mice were drinking from the time of wounding appeared to initially result in reduced erosion frequency (15% vs 40%), differences between control mice and those on dox supplemented water were not seen at later time points. Furthermore, mice given dox beginning 2 wk after wounding, showed no differences in erosion frequency when compared to control mice. Data show that the frequency of spontaneous erosions after 2.5 mm debridement wounds is not reduced by treatment of mice with oral doses of doxycycline. It remains to be determined whether higher or lower doses of doxycycline than those tried here, or topical application of tetracyclines or their derivatives could improve healing.
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