RESUMEN
Objective. Corneal neovascularization is a sight-threatening condition affecting more than 1.4 million people per year. Left untreated, it can lead to tissue scarring, oedema, lipid deposition, and persistent inflammation that may significantly affect visual prognosis and quality of life. The aim was to review the recent evidence relating to the pathophysiology, investigations and management of corneal neovascularization. Methods. Literature review of prospective and retrospective studies, clinical trials and animal models relating to the pathophysiology, investigation and management of corneal neovascularization. Results. Corneal neovascularization is characterized by the invasion of new blood vessels into the cornea caused by an imbalance between angiogenic and antiangiogenic factors that preserve corneal transparency as a result of various ocular insults and hypoxic injuries. Risk factors that have been implicated in the pathogenesis of the disease include contact lens wear, ocular surface disease, trauma, previous surgery and herpes. The results highlighted the current and future management modalities of corneal neovascularization, which includes corneal transplantation, laser - phototherapy, injections and topical treatment. Conclusion. The future of corneal neovascularization is promising and this paper discusses the upcoming revolution in local gene therapy. Abbreviations. HSK = herpes stromal keratitis, VEGF = vascular endothelial growth factor, VEGFR-1 = VEGF Receptor-1, FGF = Fibroblast growth factor, PDGF = Platelet-derived growth factor, IL-6 = interleukin-6, IL-7 = interleukin-7, IL-8 = interleukin-8, IRS-1 = insulin receptor substrate-1.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Córnea/irrigación sanguínea , Neovascularización de la Córnea , Manejo de la Enfermedad , Terapia Genética/métodos , Queratoplastia Penetrante/métodos , Agudeza Visual , Animales , Córnea/patología , Neovascularización de la Córnea/diagnóstico , Neovascularización de la Córnea/fisiopatología , Neovascularización de la Córnea/terapia , HumanosRESUMEN
PURPOSE: To evaluate the effect of orally administered sorafenib on corneal neovascularization in rat models. METHODS: In male Sprague-Dawley rats, a silver nitrate applicator was placed on the central cornea in both eyes to elicit angiogenesis. Rats were divided into 3 groups, the control group and the 2 sorafenib-treated groups (low dose, 30 mg · kg(-1) · day(-1); high dose, 60 mg · kg(-1) · day(-1)). The area of corneal neovascularization was measured by image analysis. Vascular endothelial growth factor receptor 2 (VEGFR2) messenger RNA expression was measured in rat corneas by reverse transcription-polymerase chain reaction, and the expression of phosphorylated extracellular signal-regulated kinase (ERK) was measured by Western blot analysis 1 week after cauterization. RESULTS: The area of corneal neovascularization was significantly reduced by 44% in the 30 mg · kg(-1) · day(-1) group and by 66% in the 60 mg · kg(-1) · day(-1) group, compared with the control group (P = 0.014 and P < 0.0001). Corneal VEGFR2 messenger RNA expression was higher in the control group than in the sorafenib-treated groups. The expression of phosphorylated ERK in rat corneas was suppressed in the sorafenib-treated groups but not in the control group. CONCLUSIONS: Oral administration of a multikinase inhibitor (sorafenib) significantly reduced the development of experimental corneal neovascularization in a dose-dependent manner. This inhibitory effect is probably related to the suppression of ERK phosphorylation by sorafenib.