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Marion K Gordon, Andrea DeSantis Rodrigues, Rita A Hahn, Peihong Zhou, Donald R Gerecke, Adele Miller, Kathy K H Svoboda, ; Doxycycline, AminoPlex and a Retro Olvanil Hydroxamate Reduce pEGFR Levels after Mustard Exposure and Improve Corneal Wound Healing. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):714.
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Sulfur mustard (SM), nitrogen mustard (NM) and half mustard (CEES) are chemical agents that disrupt the basement membrane zone of cornea and skin. Our goal is to develop therapies to treat ocular injury resulting from mustard exposure. Although the phenotype of mustard exposure has been characterized for 100 years now, the affected cellular mechanisms are not fully characterized. Without understanding the responses of corneal cells to mustard, the development of therapies has been impeded.
Rabbit corneal organ cultures were exposed to NM for 2 hr, then incubated for an additional 22 hr with or without doxycycline, aminoplex, or a retroolvanil hydroxamate therapy, applied 4 times over the course of 22 hrs. After incubation, Epidermal Growth Factor (EGF) and phosphorylated EGFR levels were assessed by immunofluorescence, and compared with histologic appearance.
Results: Epidermal Growth Factor (EGF) and phosphorylated EGFR (pEGFR) were assessed in sections of mustard-exposed corneas, and were found to be highly expressed by IF. When corneas were treated with either doxycycline, tobradex, aminoplex, or the retro-olvanil hydroxamate 4 times over the course of the 22 hrs, starting at 2 hr after NM exposure, the level of pEGFR was greatly reduced as compared to corneas receiving no therapy. In addition, their histologic phenotype was improved.
Conclusions: The reduced level of pEGFR in the therapy-treated corneas correlated with wound repair. This suggests that EGF perhaps may not be an ideal mustard therapy for the intact cornea or skin, as suggested by Henemyre-Harris et al, Eplasty8:e16, 2008. However, experimentation using a direct EGF or pEGFR inhibitor needs to be done to verify this.
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