دراسة الآليات الفيزيولوجية المرض ضمور العصب البصري الراجح

Abstract

ABSTRACT Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC) and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Two genes (OPA1, OPA3) encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8) are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7) are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins are embedded in the inner membrane and ubiquitously expressed. Optic nerve degeneration is therefore due to disturbed mitochondrial function. However, the trigger for RGC loss is much more complex than a simple bioenergetic crisis. More than 200 mutations in the OPA1 gene have been found to cause optic atrophy type 1 (Dominant form). The most conmen mutation in this gene is R445H. While, a nonsense mutation in the TMEM126A gene which is also known as OPA7 has been shown to be related to optic atrophy type 7 (receive form). A set of different aspects of optic nerve atrophy had been studied in this work, where a search for mutations in the gene TMEM 126A took place with a group of patients and all samples illustrated negative results. Then a search for quality and quantity mutations in mitochondrial DNA concerning a group of mice with genotype OPA1 +/- where carried out and results showed no relationship between the mutation on OPA1 and mitochondrial DNA. Finally in this thesis we studied the impact of Genistein as an anti-oxidant on the fibroblast cells obtained from patients carrying the mutation R445H OPA1, where it was found that this product have a positive impact in increasing cell viability, a slight improvement in the structure of the network and an effect on the mitochondrial membrane potential