RESUMEN
Cell proliferation and related cellular behavior in ocular neoplastic disease and in the healing process in ocular surgery or post-injury management, as well as new treatment strategy were investigated. The roles of growth factors and their signal transduction pathways were studied. Cell proliferation-related signals were found to be activated to a greater extent in malignant ocular tumors than in benign tumor cells regardless of the similarity of simple histological findings. Suppression of cell proliferation-related signals can be a new treatment for ocular neoplastic diseases. The causes of complications associated with tissue repair response include acceleration of cell proliferation and extracellular matrix expression and cellular phenotypic alteration, i. e., epithelial-mesenchymal transition. These cellular activities can be controlled by modulation of growth factor signaling by employing such strategy including gene introduction.
Asunto(s)
Proliferación Celular , Transducción de Señal/genética , Transducción de Señal/fisiología , Proteínas Smad/fisiología , Factor de Transcripción AP-1/fisiología , Factor de Crecimiento Transformador beta/fisiología , Animales , Neoplasias del Ojo/patología , Neoplasias del Ojo/terapia , Regulación del Desarrollo de la Expresión Génica , Terapia Genética , Proteínas Hedgehog , Humanos , Fenómenos Fisiológicos Oculares , Transactivadores/fisiología , Cicatrización de Heridas/genética , Cicatrización de Heridas/fisiologíaRESUMEN
PURPOSE: To investigate the effect of tetrandrine on activation of human subconjunctival fibroblasts (SCFs) in vitro. METHODS: Effects of tetrandrine on proliferation, matrix expression, myofibroblast generation, and cell migration of SCF were examined in SCF cultures. Tetrandrine effect on TGFbeta 1/Smad2 signal and Smad7 expression was examined. Migration was evaluated by in vitro defect closure in a monolayer cell culture. Western blotting and immunocytochemistry were used. RESULTS: Tetrandrine suppressed wound-induced cell migration (defect closure) and myofibroblast generation, but not cell proliferation in SCF cultures. It also decreased expression of fibronectin, collagen I, and alpha SMA. Adding tetrandrine increased protein level of Smad7 and suppressed Smad2 signal. CONCLUSION: Tetrandrine suppresses Smad2 signal and fibrogenic responses in SCFs in association with Smad7 up-regulation, suggesting its potential therapeutic value to prevent excess scarring/fibrosis in conjunctiva following trabeculectomy or in patients with severe conjunctival inflammation.
Asunto(s)
Bencilisoquinolinas/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Conjuntiva/citología , Medicamentos Herbarios Chinos/farmacología , Fibroblastos/efectos de los fármacos , Inmunosupresores/farmacología , Actinas/metabolismo , Western Blotting , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Ensayo de Inmunoadsorción Enzimática , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Proteína Smad2/metabolismo , Proteína smad7/metabolismo , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
PURPOSE: To examine the effect of topical administration of mitomycin C (MMC) on the opacification of residual anterior lens capsule in a vitrectomized/lensectomized eye. METHODS: Adult Japanese albino rabbits ( n=8) received two-port vitrectomy and lensectomy with or without topical administration of MMC (0.4 mg/ml) to the residual anterior lens capsule in one eye under both general and topical anesthesia. Four eyes after vitrectomy and lensectomy were exposed to MMC for 1 min and washed out with balanced salt solution. After 1 month, the anterior segment of each globe was observed with EAS-1000 in vivo under general anesthesia and then the enucleated globes were observed through the Miyake view. Histological examination was performed. RESULTS: During healing intervals in eyes without MMC exposure, regenerated lens structure of Soemmering's ring or fibrous tissue was formed in peripheral or central areas of the residual capsule, respectively. Both the anterior lens capsule opacification and lens fiber regeneration were statistically significantly reduced by MMC topical exposure. CONCLUSION: Lens epithelial cells produce regenerated lenticular structure and fibrous tissue on the residual capsule following vitrectomy and lensectomy in rabbits. Exposure of the residual anterior capsule to MMC may be effective in reducing both its opacification and lens fiber regeneration after vitrectomy/lensectomy.