Retinoic Acid Improves Ciliogenesis after Surgery of the Maxillary Sinus in Rabbits

Abstract

Retinoids have been shown to be important cofactors in regulating the differentiation and proliferation of ciliated epithelial cells of the respiratory tract. In particular, retinoic acid has been shown to enhance the regeneration of paranasal sinus mucosa. The objective of this study is to use scanning electron microscopy techniques to evaluate the effect of topical retinoic acid on mucosal wound healing in a rabbit model of maxillary sinus surgery. It is hypothesized that the application of topical retinoic acid will enhance ciliogenesis and improve the morphology of regenerated cilia compared with controls. Prospective multi-arm controlled animal trial. Eighteen New Zealand white rabbits underwent surgical opening of the maxillary sinuses through a midline incision. The rabbits were divided among four experimental groups: 1) mucosal stripping alone (stripped control), 2) stripping followed by topical application of an inert aqueous gel, 3) stripping followed by application of 0.01% retinoic acid in aqueous gel, and 4) no mucosal stripping and no topical treatment (nonstripped control). After 14 days, the medial wall of the maxillary sinus was harvested and examined by scanning electron microscopy at x2,000 and x5,000 magnification. The micrographs were then rated by a blinded review panel for ciliary density, orientation, and morphology. Mean scores for ciliary density, orientation, and morphology were all significantly higher for the retinoic acid treatment group compared with both the inert aqueous gel treatment group and the stripped control group (P=.004-.03 for all comparisons, Student's t test). Mean scores for the retinoic acid treatment group were numerically lower than the nonstripped control group but did not approach statistical significance for any parameter (P=.23-.31). In a rabbit model of maxillary sinus surgery, topically delivered retinoic acid enhances ciliogenesis. Qualitative assessment of ciliary density, orientation, and morphology shows improved healing in retinoic acid treated sinuses compared with both untreated control sinuses and aqueous gel treated sinuses.