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G. P. Holley, J. M. Miller, R. J. McCulloh, H. F. Edelhauser, P. E. Miller, C. J. Murphy, B. J. Christian, P. B. Smith, T. T. Lam; The Effect of Topically Applied Mitomycin C on Cynomolgus Monkey Corneal Endothelium. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3954.
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To evaluate the effect on the corneal endothelium of 0.2% Mitomycin C (MMC) applied topically to monkey corneas using two different in vivo specular microscopes (contact and noncontact) and to compare to ex vivo Alizarin Red staining.
Ten Cynomolgus monkeys (under anesthesia) received a single topical application to the central cornea for 2 minutes using sterile gauze: In Group 1 (n=5), both eyes received 0.9% saline with the OD central corneal epithelium debrided (8 mm) using a corneal gill knife and the OS eye serving as a control. In Group 2 (washed with BSS after dosing, n=5) both eyes received 0.2% MMC with the OD cornea debrided and the OS cornea serving as MMC control (no debride.). Specular microscopy (Topcon SP-3000 noncontact and a Keeler-Konan SP-1 contact) was performed on these corneas before dosing and on day 15. Animals were euthanized on day 16 and central corneas were removed and the corneal endothelium was stained with 0.1% Alizarin Red dye for 7 minutes. Endo. cell density (ECD), avg.cell area, coeff. of variation of cell area (CV), % Hexagons, and # of cells counted were determined.
Comparing the values of ECD, % hexagons, and CV at day 1 and day 15, there were no significant changes in the three control groups. However, there was a very significant drop (36.1% to 50.6%) in ECD in group 2 (MMC/debrided) by day 15 recorded by both specular microscopy techniques (noncontact p value=0.0017, contact p value=0.032) and alizarin red staining (p value=0.0017). There was also a significant difference in % hexagons in group 2 (MMC/debrided versus MMC/nondebrided) on day 15/16 in all 3 techniques. Additionally, there was a significant difference in CV in alizarin red stained corneas in group 2 (MMC/debrided versus MMC/nondebrided).
Topically applied 0.2% MMC coupled with a debrided epithelium had a highly significant deleterious effect on monkey corneal endothelium measured by contact and noncontact specular microscopy and ex vivo alizarin red staining.
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