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Marion K Gordon, Andrea DeSantis Rodrigues, Iris Po, Rita Hahn, Donald Gerecke, Kathy K H Svoboda; Equivalent UVB-induced and NM-induced corneal injuries heal at different speeds over the course of 7 days post exposure. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4697.
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© ARVO (1962-2015); The Authors (2016-present)
We have observed that UVB corneal injuries heal faster than equivalent nitrogen mustard (NM)-induced wounds. Our overall goal is to elucidate what mechanisms that are involved in the delay of corneal wound healing after mustard injury.
Rabbit corneal organ cultures were exposed to nitrogen mustard (NM) or UVB at doses that result in 60% epithelial-stromal separation at 24 hr post exposure. Corneal cultures were allowed to heal for 7 days, then were processed for H and E staining, immunofluorescence, and Western blot analysis .
UVB-exposed corneas reestablished epithelial-stromal integrity within 7 days of exposure, but equivalent corneal injury due to NM exposure was only partially healed by 7 days. In areas where the epithelial-stromal junction was reestablished in NM-exposed corneas, the number of fibroblasts residing in the anterior stroma after 7 days was greatly reduced, and repopulation lagged behind that of UVB-treated corneas. Local areas where the epithelial-stromal junction was imperfectly reformed were often observed in NM-exposed corneas, but not in UVB exposed corneas at 7 days post exposure. Immunofluorescence analysis of organ cultured corneas demonstrated that the expression of the furin was still elevated 7 days after NM exposure. Interestingly, ADAMTS4 was expressed in UVB-exposed corneas for 3 days after exposure, while in NM-exposed corneas ADAMTS4 persisted for 5 days after exposure. The expression level of the enzyme was about 5 times greater in NM-exposed than in UVB treated corneas.
The difference in healing time of equivalent corneal injuries induced by NM-exposure versus UVB-exposure may be related to the extended activity of enzymes like furin and ADAMTS4.
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