High resolution imaging of epithelial injury in the sheep cervicovaginal tract: A promising model for testing safety of candidate microbicides

Kathleen Vincent, Nigel Bourne, Brent A. Bell, Gracie Vargas, Alai Tan, Daniel Cowan, Lawrence R. Stanberry, Susan L. Rosenthal, Massoud Motamedi

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

BACKGROUND:: Access to readily available large animal models and sensitive noninvasive techniques that can be used for the evaluation of microbicide-induced changes in tissue could significantly facilitate preclinical evaluations of microbicide safety. The sheep cervicovaginal tract, with stratified squamous epithelium similar to humans, holds promise as a large animal model used before nonhuman primates. In addition, optical coherence tomography (OCT) could enable high resolution visualization of tissue morphology and noninvasive assessment of microbicide-induced epithelial injury. METHODS:: We evaluated the dose response of sheep cervicovaginal tract to benzalkonium chloride (BZK). Twenty sheep received treatment with phosphate-buffered saline or BZK solution (2%, 0.2%, or 0.02%). Pre- and posttreatment colposcopy and OCT images were collected and graded based on World Health Organization criteria and a previously reported scoring system, respectively. Biopsies were collected and the degree of epithelial injury and its thickness was assessed based on histology and OCT. RESULTS:: The sheep cervicovagina exhibited anatomic and microscopic features similar to the human. Extensive loss of the epithelium was noted on colposcopy and OCT after application of 2% BZK. Colposcopy detected findings in half of sheep and OCT in all sheep treated with 0.2% BZK. OCT detected differences in the 0.02% BZK-treated group compared with controls, whereas colposcopy failed to detect any changes. CONCLUSIONS:: The sheep cervicovagina is similar to humans, and exhibits dose dependent epithelial changes after BZK treatment. These findings suggest that the sheep model and OCT may become valuable tools for the safety evaluation of candidate microbicides, and warrant continued development.

Original languageEnglish (US)
Pages (from-to)312-318
Number of pages7
JournalSexually Transmitted Diseases
Volume36
Issue number5
DOIs
StatePublished - May 2009

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Benzalkonium Compounds
Anti-Infective Agents
Optical Coherence Tomography
Sheep
Safety
Colposcopy
Wounds and Injuries
Epithelium
Animal Models
Primates
Histology
Phosphates
Biopsy
Therapeutics

ASJC Scopus subject areas

  • Dermatology
  • Public Health, Environmental and Occupational Health
  • Microbiology (medical)
  • Infectious Diseases

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High resolution imaging of epithelial injury in the sheep cervicovaginal tract : A promising model for testing safety of candidate microbicides. / Vincent, Kathleen; Bourne, Nigel; Bell, Brent A.; Vargas, Gracie; Tan, Alai; Cowan, Daniel; Stanberry, Lawrence R.; Rosenthal, Susan L.; Motamedi, Massoud.

In: Sexually Transmitted Diseases, Vol. 36, No. 5, 05.2009, p. 312-318.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND:: Access to readily available large animal models and sensitive noninvasive techniques that can be used for the evaluation of microbicide-induced changes in tissue could significantly facilitate preclinical evaluations of microbicide safety. The sheep cervicovaginal tract, with stratified squamous epithelium similar to humans, holds promise as a large animal model used before nonhuman primates. In addition, optical coherence tomography (OCT) could enable high resolution visualization of tissue morphology and noninvasive assessment of microbicide-induced epithelial injury. METHODS:: We evaluated the dose response of sheep cervicovaginal tract to benzalkonium chloride (BZK). Twenty sheep received treatment with phosphate-buffered saline or BZK solution (2{\%}, 0.2{\%}, or 0.02{\%}). Pre- and posttreatment colposcopy and OCT images were collected and graded based on World Health Organization criteria and a previously reported scoring system, respectively. Biopsies were collected and the degree of epithelial injury and its thickness was assessed based on histology and OCT. RESULTS:: The sheep cervicovagina exhibited anatomic and microscopic features similar to the human. Extensive loss of the epithelium was noted on colposcopy and OCT after application of 2{\%} BZK. Colposcopy detected findings in half of sheep and OCT in all sheep treated with 0.2{\%} BZK. OCT detected differences in the 0.02{\%} BZK-treated group compared with controls, whereas colposcopy failed to detect any changes. CONCLUSIONS:: The sheep cervicovagina is similar to humans, and exhibits dose dependent epithelial changes after BZK treatment. These findings suggest that the sheep model and OCT may become valuable tools for the safety evaluation of candidate microbicides, and warrant continued development.",
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