May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
The Effect of Topically Applied Mitomycin C on Cynomolgus Monkey Corneal Endothelium
Author Affiliations & Notes
  • G. P. Holley
    Toxicology, Covance Laboratories, Madison, Wisconsin
  • J. M. Miller
    Toxicology, Covance Laboratories, Madison, Wisconsin
  • R. J. McCulloh
    Toxicology, Covance Laboratories, Madison, Wisconsin
  • H. F. Edelhauser
    Ophthalmology, Emory University, Atlanta, Georgia
    Comparative Ophthalmic Research Labs, Madison, Wisconsin
  • P. E. Miller
    Comparative Ophthalmic Research Labs, Madison, Wisconsin
  • C. J. Murphy
    Comparative Ophthalmic Research Labs, Madison, Wisconsin
  • B. J. Christian
    Toxicology, Covance Laboratories, Madison, Wisconsin
  • P. B. Smith
    Toxicology, Covance Laboratories, Madison, Wisconsin
  • T. T. Lam
    Toxicology, Covance Laboratories, Madison, Wisconsin
  • Footnotes
    Commercial Relationships  G.P. Holley, None; J.M. Miller, None; R.J. McCulloh, None; H.F. Edelhauser, None; P.E. Miller, None; C.J. Murphy, None; B.J. Christian, None; P.B. Smith, None; T.T. Lam, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3954. doi:
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    • Get Citation

      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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose:
 

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.

 
Methods:
 

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.

 
Results:
 

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).  

 
Conclusions:
 

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.

 
Keywords: cornea: endothelium • drug toxicity/drug effects • cornea: basic science 
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