Comparison of Prostaglandin Analog Exposure on Wound Healing Response in the Porcine Model

1
Comparison of Prostaglandin Analog Exposure on
Wound Healing Response in the Porcine Model

• Mark McDermott, Fu-Shin X. Yu, Jia Yin,Ashok
  Kumar, Ke-Ping Xu
• Kresge Eye InstituteWayne State University,
  Detroit, MI

This study was funded by an unrestricted grant
from Allergan, Inc.The authors have no financial
relationships to disclose.
2
Abstract

• Purpose To determine the effect of prostaglandin
  analog exposure on corneal wound healing.
• Methods Standardized 5 mm epithelial wounds were
  made with ex vivo whole globe porcine eyes (n
  3). Globes were incubated for 24 hours in MEM
  before topical administration of 30 µL of test
  agents (saline control, toxic control Triton,
  Travatan Z, Travatan, Lumigan, and Xalatan).
  Wounds were exposed for 10 minutes to test agent,
  rinsed twice with 3 mL PBS, and subsequently 2 mL
  fresh MEM were added.Forty-eight hours
  postincision, wound healing response and
  epithelial defects were evaluated by staining
  (Richardsons staining solution).
• Results Forty-eight hours after 5-mm incision,
  corneoepithelial wounds had a mean healed
  percentage of baseline saline control 96.89,
  toxic control 6.06, Lumigan 97.32,
  Travatan 84.76, Travatan Z 99.80, and
  Xalatan 80.51. The wound size differences of
  Lumigan, Travatan and Travatan Z were not
  statistically significant from the saline control
  (P .260, P .141, P .278 respectively).
  Xalatan statistically significantly delayed
  wound closure compared to saline control,
  Lumigan, and Travatan Z (P lt .001 and P lt .001,
  respectively).
• Conclusion The ex vivo porcine model permits the
  quantitative assessment of the impact of
  pharmaceutical agents on corneoepithelial wound
  healing. Lumigan and Travatan Z did not delay
  wound healing response rates. The effect of
  antihypertensive treatment on wound healing
  should be considered for patients following
  glaucoma filtration and/or cataract surgery.

3
Introduction

• Exposure of corneal epithelial cells to irritants
  can trigger a cellular stress response, altering
  expression of factors involved in initiation of
  wound healing.
• Ocular irritancy of ophthalmic medications in
  humans can be predicted using ex vivo models.1
• In a bovine cornea model, benzalkonium chloride
  (BAK) and sodium dodecyl sulfate (SDS)
• Induced tight junction disruption, increased
  permeability of corneal epithelium, and caused
  breakdown of epithelial barrier
• Altered dose- and time-dependent binding activity
  of transcription factors (eg, AP-1 and NF?B)
• A porcine cornea model is introduced to evaluate
  ophthalmic medication tolerability and toxicity
  on epithelial wound healing.

1. Xu et al. Toxicol Sci. 2000 58306-314.
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Purpose

• To determine the effect of prostaglandin analog
  exposure on corneal wound healing.

5
Methods

• Standardized 5-mm epithelial wounds were made
  with ex vivo whole globe porcine eyes (n 3).
• Globes were incubated for 24 hours in minimum
  essential medium (MEM) before topical
  administration of 30 µL of test agents
• Saline control
• Toxic control (Triton)
• Travatan Z (travoprost 0.004 sofZiaTM Alcon
  Laboratories, Inc. Fort Worth, TX)
• Travatan (travoprost 0.004 0.015 BAK Alcon
  Laboratories, Inc. Fort Worth, TX)
• Lumigan (bimatoprost 0.03 0.005 BAK
  Allergan, Inc. Irvine, CA)
• Xalatan (latanoprost 0.005 0.02 BAK Pfizer,
  Inc. New York, NY)
• Wounds were exposed for 10 minutes to test agent,
  rinsed twice with3 mL PBS and subsequently 2 mL
  fresh MEM were added.
• Wound healing response and epithelial defects
  were evaluated by staining (Richardsons staining
  solution) 48 hours postincision.

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Corneoepithelial Wound Healing
7
Corneoepithelial Wound Healing

Control
Triton
Lumigan
Travatan
Travatan Z
Xalatan

• Wound healing with Lumigan, Travatan, and
  Travatan Z did not differ significantly from
  control.

Significantly (P lt .001) delayed healing
compared with control, Lumigan, and Travatan Z.
8
Discussion

• Wound healing response in porcine eyes differs
  among the PGAs evaluated.
• This may be dependent on a combination of the
  active ingredient and the preservative.

9
Conclusion

• The ex vivo porcine model permits the
  quantitative assessment of the impact of
  pharmaceutical agents on corneoepithelial wound
  healing.
• Lumigan, Travatan, and Travatan Z did not
  delay wound healing response rates, while wound
  healing was delayed with Xalatan.
• The effect of IOP-lowering agents on wound
  healing may be a consideration for patients
  following glaucoma filtration or cataract
  surgery.