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

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 Institute Wayne State University, Detroit, MI .

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

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  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 (Richardson’s 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 < .001 and P < .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; 58:306-314.

  4. 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 (Richardson’s staining solution) 48 hours postincision.

  6. Original wound 48 hours post-wounding Control Triton X-100 Lumigan® Travatan® Travatan Z® Xalatan® Corneoepithelial Wound Healing

  7. Corneoepithelial Wound Healing • Wound healing with Lumigan®, Travatan®, and Travatan Z® did not differ significantly from control. * Control Triton Lumigan® Travatan® Travatan Z® Xalatan® *Significantly (P < .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.

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