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S. Pal–Ghosh, R.A. Jurjus, Y. Liu, G. Tadvalkar, M. Stepp; Reduced Frequency of Spontaneous Erosions After Corneal Debridement Wounding in Syndecan–1 Null Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2756.
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When 8 wk old Balb/c mice are subjected to large (2.5 mm) manual debridement wounds to their cornea, all the wounds close initially, but recurrent erosions develop spontaneously at later times with high frequency and a partial corneal epithelial stem cell deficiency develops. To determine whether mice lacking the heparan sulfate proteoglycan syndecan–1 (sdc–1) are also subject to recurrent erosions and stem cell deficiency, similar experiments were carried out in sdc–1 null mice.
Sdc–1 null mice are maintained on a Balb/c genetic background obtained by serial backcrosses (7) with Balb/cJ mice. 2.5 mm wounds were made to the eyes of 8 wk old sdc–1 null mice (n= 32 eyes) and wildtype control Balb/c mice (n=38 eyes). Eyes were evaluated for evidence of erosions at 2, 4, 6, and 8 wks after wounding using fluorescein eye drops. After 8 wk, all mice were sacrificed, a suture was placed in the temporal sclera of each eye, the left and right eyes were separated and labeled, and all eyes were processed for whole mount immunofluorescence microscopy.
At 2, 4, 6, and 8 wk after wounding, 66%, 97%, 92%, and 73% of the eyes of the wildtype mice showed evidence of erosions. By contrast, 41%, 47%, 47%, and 50% of the 32 eyes of the sdc–1 null mice had visible erosions at 2, 4, 6, and 8 wk after wounding. Differences in erosion frequency between wildtype and sdc–1 null mice were significant at all time points studied.
Normal mice develop spontaneous erosions after 2.5 mm manual debridement wounds with the erosion frequency highest at 4 and 6 wk after wounding. The majority of these eyes show evidence of partial stem cell deficiency as seen by the presence of goblet cells in the central cornea. In contrast, sdc–1 null mice show significantly fewer erosions after wounding. Furthermore, unlike wildtype mice, the frequency of erosions did not change significantly from 2 through 8 wk but remained similar at all time points studied. It will be interesting to determine whether or not the sdc–1 null mice also show evidence of stem cell deficiency. These data indicate that while the sdc–1 null mice initially heal corneal debridement wounds at a slower rate than wildtype mice, their ocular surface, once healed, is more stable and less likely to develop erosions spontaneously.
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