ABSTRACT
We investigated the bioavailability and stability of a C-Clear artificial cornea in a rabbit chemical burn model. Thirty-six rabbits were divided into a control group (n = 16) and a chemical burn group that used NaOH solution (n = 20). After lamellar dissection, the central posterior lamella was excised using a 3 mm diameter trephine, and an artificial cornea was transplanted into the lamellar pocket. After 2 weeks, the central anterior lamella was excised using a 3 mm diameter trephine to secure a clean visual axis. We examined the anterior segment of the eyes weekly for 12 weeks after transplantation. Successful subjects whose artificial corneas were maintained stably for 12 weeks were euthanized and underwent histologic examinations. Artificial corneas remained stable for up to 12 weeks in 62.5 and 50% of rabbits in the control and chemical burn groups, respectively. Two rabbits in the chemical burn group showed the formation of a retroprosthetic membrane, and one rabbit with visual axis blockage underwent membrane removal using a Nd:YAG laser. In histologic examinations, adhesion between artificial cornea and peripheral corneal stoma was observed. In conclusion, we confirmed structural stability and biocompatibility of the C-Clear artificial cornea for up to 12 weeks after implantation in control and chemical burn groups.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Collagen/metabolism , Fibroblasts/drug effects , Pyrimidinones/pharmacology , Skin/drug effects , Wnt Signaling Pathway/drug effects , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Cicatrix, Hypertrophic/drug therapy , Cicatrix, Hypertrophic/pathology , Drug Evaluation, Preclinical , Fibroblasts/metabolism , Humans , Keloid/drug therapy , Keloid/pathology , Keloid/surgery , Primary Cell Culture , Pyrimidinones/therapeutic use , Skin/cytology , Skin/metabolismABSTRACT
BACKGROUND: Wnt/ß-catenin signaling is important in development and differentiation of melanocytes. OBJECTIVE: The object of this study was to evaluate the effects of several Wnt/ß-catenin signaling inhibitors on pigmentation using melanoma cells. METHODS: Melanoma cells were treated with Wnt/ß-catenin signaling inhibitors, and then melanin content and tyrosinase activity were checked. RESULTS: Although some inhibitors showed slight inhibition of pigmentation, we failed to observe potential inhibitory effect of those chemicals on pigmentation of HM3KO melanoma cells. Rather, one of powerful Wnt/ß-catenin signaling inhibitors, ICG-001, increased the pigmentation of HM3KO melanoma cells. Pigmentation-enhancing effect of ICG-001 was reproducible in other melanoma cell line MNT-1. Consistent with these results. ICG-001 increased the expression of pigmentation-related genes, such as MITF, tyrosinase and TRP1. When ICG-001 was treated, the phosphorylation of CREB was significantly increased. In addition, ICG-001 treatment led to quick increase of intracellular cAMP level, suggesting that ICG-001 activated PKA signaling. The blockage of PKA signaling with pharmaceutical inhibitor H89 inhibited the ICG-001-induced pigmentation significantly. CONCLUSIONS: These results suggest that PKA signaling is pivotal in pigmentation process itself, while the importance of Wnt/ß-catenin signaling should be emphasized in the context of development and differentiation.
