ABSTRACT
Los traumatismos oculares representan la principal causa de pérdida de la agudeza visual en individuos jóvenes y se sitúa entre las causas de ceguera en el mundo. Pueden tener un efecto devastador sobre el globo ocular; es el tipo de traumatismo más severo en esta zona, con un pobre pronóstico visual para el paciente. Constituye un accidente grave, que en muchas ocasiones conlleva a la enucleación. Se presentan tres pacientes con rotura del globo ocular, con la conducta terapéutica, seguimiento y resultados visuales en cada caso, para mostrar a la comunidad médica, la complejidad y particularidades de este traumatismo(AU)
Ocular traumatisms represent the principal cause of loss of vision in young people and they are among the causes of blindness in the world. Trauma can result in a wide spectrum of tissue lesions of the globe and it can has devastating effect on the eyeball, since it is the most severe type of trauma in this area, with a poor visual prognosis for the patient. It is a serious accident, which often leads to nucleation as result of a bruised intense trauma. This is the report of three patients with rupture of the ocular globe with the therapeutic behavior, follow-up and visual results in each case, to show the medical community, the complexity and particularities of this traumatism(AU)
Subject(s)
Humans , Male , Female , Adult , Aged , Vitrectomy/methods , Eye Enucleation/methods , Eye Injuries, Penetrating/surgery , Tomography, Spiral Computed/methods , Vitreoretinopathy, Proliferative/drug therapyABSTRACT
OBJECTIVE@#This paper applied a transcriptomic approach to investigate the mechanisms of adriamycin (ADR) in treating proliferative vitreoretinopathy (PVR) using ARPE-19 cells.@*METHODS@#The growth inhibitory effects of ADR on ARPE-19 cells were assessed by sulforhodamine B (SRB) assay and propidium iodide (PI) staining using flow cytometry. The differentially expressed genes between ADR-treated ARPE-19 cells and normal ARPE-19 cells and the signaling pathways involved were investigated by microarray analysis. Mitochondrial function was detected by JC-1 staining using flow cytometry and the Bcl-2/Bax protein family. The phosphorylated histone H2AX (γ-H2AX), phosphorylated checkpoint kinase 1 (p-CHK1), and phosphorylated checkpoint kinase 2 (p-CHK2) were assessed to detect DNA damage and repair.@*RESULTS@#ADR could significantly inhibit ARPE-19 cell proliferation and induce caspase-dependent apoptosis in vitro. In total, 4479 differentially expressed genes were found, and gene ontology items and the p53 signaling pathway were enriched. A protein-protein interaction analysis indicated that the TP53 protein molecules regulated by ADR were related to DNA damage and oxidative stress. ADR reduced mitochondrial membrane potential and the Bcl-2/Bax ratio. p53-knockdown restored the activation of c-caspase-3 activity induced by ADR by regulating Bax expression, and it inhibited ADR-induced ARPE-19 cell apoptosis. Finally, the levels of the γ-H2AX, p-CHK1, and p-CHK2 proteins were up-regulated after ADR exposure.@*CONCLUSIONS@#The mechanism of ARPE-19 cell death induced by ADR may be caspase-dependent apoptosis, and it may be regulated by the p53-dependent mitochondrial dysfunction, activating the p53 signaling pathway through DNA damage.
Subject(s)
Humans , Apoptosis , Caspases/metabolism , Cell Proliferation , Cell Survival/drug effects , Doxorubicin/pharmacology , Flow Cytometry , Gene Expression Profiling , Gene Expression Regulation , Membrane Potential, Mitochondrial , Oligonucleotide Array Sequence Analysis , Oxidative Stress/drug effects , Phosphorylation , Propidium/chemistry , RNA, Small Interfering/metabolism , Retinal Pigment Epithelium/metabolism , Rhodamines/chemistry , Signal Transduction/drug effects , Transcriptome , Tumor Suppressor Protein p53/metabolism , Vitreoretinopathy, Proliferative/drug therapyABSTRACT
Proliferative vitreoretinopathy (PVR) remains the most common cause of failure in retinal detachment surgery. Surgical procedures for its repair entails complex and extensive instrumentation besides technical skill. The success rate varies widely with high incidence of redetachment. Keeping this in view, we evaluated the role of intravitreal daunorubicin as an anti-mitiotic agent in the inhibition of PVR. Our study concluded that 5 micrograms of intravitreal daunorubicin effectively inhibited PVR in the rabbit eye and the dosage was safe and nontoxic. The half-life of the drug was determined to be about 140 minutes, suggesting a prolonged intravitreal concentration sufficient to prevent fibroblast proliferation.