Effects of all-trans retinoic acid nanoparticles on corneal epithelial wound healing

We have developed inorganically-coated all-trans retinoic acid (atRA) nanoparticles, nano-sized egg-like particles of atRA (NANOEGGA (R)-atRA). The purpose of this study was to determine the effects of NANOEGGA (R)-atRA on corneal wound healing in vivo and in vitro. A rabbit corneal epithelial wound healing model was exposed to different concentrations of NANOEGGA (R)-atRA. Wound healing was serially quantified as the ratio of fluorescein-stained area at the selected times to that at baseline. After wound closure, the barrier function of the cornea was determined using low concentrations of tropicamide. At the completion of the experiments, the corneal epithelium was histologically examined. For the in vitro studies, linear scratch wounds were made on cultured SV40-immortalized human corneal epithelial cells (HCE-T). Then, the cells were exposed to different concentrations of NANOEGGA (R)-atRA, and wound healing was determined by the degree of closure of the scratch wound. In addition, the effects of NANOEGGA (R)-atRA on the proliferation of HCE-T cells were determined by WST-8 assays. Exposure to NANOEGGA (R)-atRA decreased the injured area 24 hrs after the ablation. The maximum effect of NANOEGGA (R)-atRA was observed at a concentration of 33 mM. Histologically, no abnormal or differentiated corneal epithelial cells were observed in the histological sections treated with NANOEGGA (R)-atRA. The tropicamide-induced pupillary dilation was significantly slowed in the eyes treated with NANOEGGA (R)-atRA. NANOEGGA (R)-atRA at concentrations of 3.3 and 33 nM induced earlier wound closure in vitro, but did not induce proliferation of HCE-T cells. NANOEGGA (R)-atRA promotes wound healing and should be considered for the treatment of wounds of the corneal epithelium.