title: In Vivo Rectal Mucosal Barrier Function Imaging in a Large-Animal Model by Using Confocal Endomicroscopy: Implications for Injury Assessment and Use in HIV Prevention Studies.
abstract: Injury occurring on the surface of the rectal mucosal lining that causes defects in barrier function may result in increased risk for transmission of infection by HIV and other pathogens. Such injury could occur from microbicidal or other topical agents, mechanical trauma during consensual or nonconsensual intercourse, or inflammatory conditions. Tools for evaluation of rectal mucosal barrier function for assessing the mucosa under these conditions are lacking, particularly those that can provide in vivo structural and functional barrier integrity assessment and are adaptable to longitudinal imaging. We investigated confocal endomicroscopy (CE) as a means for in vivo imaging of the rectal epithelial barrier in the ovine model following spatially confined injury to the surface at a controlled site using a topical application of the microbicide test agent benzalkonium chloride. Topical and intravenous (i.v.) fluorescent probes were used with CE to provide subcellular resolution imaging of the mucosal surface and assessment of barrier function loss. A 3-point CE grading system based on cellular structure integrity and leakage of dye through the mucosa showed significant differences in score between untreated (1.19 ± 0.53) and treated (2.55 ± 0.75) tissue (P < 0.0001). Histological grading confirmed findings of barrier compromise. The results indicate that CE is an effective means for detecting epithelial injury and barrier loss following localized trauma in a large-animal model. CE is promising for real-time rectal mucosal evaluation after injury or trauma or topical application of emerging biomedical prevention strategies designed to combat HIV.
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, USA Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, USA grvargas@utmb.edu.
authors.forename: Gracie
authors.initials: G
authors.lastname: Vargas
authors.affiliation: Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, USA Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Kathleen Listiak
authors.initials: KL
authors.lastname: Vincent
authors.affiliation: Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: David
authors.initials: D
authors.lastname: Szafron
authors.affiliation: Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Tyra Caitlin
authors.initials: TC
authors.lastname: Brown
authors.affiliation: Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Paula Patricia
authors.initials: PP
authors.lastname: Villarreal
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Nigel
authors.initials: N
authors.lastname: Bourne
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Gregg N
authors.initials: GN
authors.lastname: Milligan
authors.affiliation: Center for Biomedical Engineering, University of Texas Medical Branch, Galveston, Texas, USA Department of Ophthalmology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Massoud
authors.initials: M
authors.lastname: Motamedi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015658:HIV Infections / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods*; D012007:Rectum / Q000166:cytology*; D012756:Sheep