RESUMO
Leber's hereditary optic neuropathy (LHON) is one of the most common mitochondrial diseases caused by point mutations in mitochondrial DNA (mtDNA). The majority of diagnosed LHON cases are caused by a point mutation at position 11,778 in the mitochondrial genome. LHON mainly affects young men in their 20s and 30s with usually poor visual prognosis. It remains unexplained why men are more likely to develop the disease and why only retinal ganglion cells are affected. In this study, a cell model was used for the first time to investigate the influence of testosterone on the cell death mechanism apoptosis and on an autophagy/mitophagy. Cells with m.11778G > A were found to be significantly more susceptible to nucleosome formation and effector caspase activation that serve as hallmarks of apoptotic cell death. Cells having this mutation expressed higher levels of mitophagic receptors BNIP3 and BNIP3L/Nix in a medium with testosterone. Moreover, cells having the mutation exhibited greater mitochondrial mass, which suggests these cells have a decreased cell survival. The observed decrease in cell survival was supported by the observed increase in apoptotic cell death. Autophagy was analyzed after inhibition with Bafilomycin A1 (Baf A1). The results indicate impairment in autophagy in LHON cells due to lower autophagic flux supported by observed lower levels of autophagosome marker LC3-II. The observed impaired lower autophagic flux in mutant cells correlated with increased levels of BNIP3 and BNIP3L/Nix in mutant cells.
Assuntos
Autofagia/efeitos dos fármacos , Mitofagia/genética , Atrofia Óptica Hereditária de Leber/tratamento farmacológico , Testosterona/farmacologia , Adulto , Apoptose/efeitos dos fármacos , Células Sanguíneas/efeitos dos fármacos , DNA Mitocondrial/genética , Feminino , Genoma Mitocondrial/genética , Humanos , Macrolídeos/farmacologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Nucleossomos/efeitos dos fármacos , Nucleossomos/genética , Atrofia Óptica Hereditária de Leber/genética , Atrofia Óptica Hereditária de Leber/metabolismo , Atrofia Óptica Hereditária de Leber/patologia , Mutação Puntual/genética , Células Ganglionares da Retina/efeitos dos fármacos , Testosterona/metabolismoRESUMO
We present a case of successful multi-procedure management of a patient with an open globe injury. A 47-year-old man sustained an injury to his left eye caused by glass fragments of his own spectacles shattered while he was protecting an unknown woman from physical assault at a bus stop. Over a span of 65 months the patient underwent multiple procedures including primary wound repair, penetrating keratoplasty combined with extracapsular cataract extraction, neodymium: YAG laser capsulotomy, and laser-assisted subepithelial keratectomy (LASEK), and had a successfully treated episode of corneal graft rejection. This sequence of treatment substantially improved his left eye vision from hand movements at the time of admission to 0.9-0.5 × 90 at the last follow-up nearly 10 years after the trauma. Proper initial surgical management of an open globe injury can create the possibility for virtually complete vision restoration.
RESUMO
PURPOSE: The aim of study is the presentation and retrospective analysis of our experience in implantations of posterior chamber lenses with transcleral fixation. MATERIAL AND METHODS: 172 eyes were analysed after implantations of posterior chamber lenses with transcleral fixation. We analysed operative technique, complications and results. RESULTS: 127 eyes obtained usable visual acuity. CONCLUSIONS: On the basis of our own observations we can say, that implantations of posterior chamber lenses with transcleral fixation is an effective and safe method in lens surgery.
