Main open-angle glaucoma (POAG) is definitely a major cause of blindness
Main open-angle glaucoma (POAG) is definitely a major cause of blindness and results from irreversible retinal ganglion cell damage and optic nerve degeneration. a single 16 487 foundation pair PCR amplicon by Ion Torrent and candidate novel variants were validated by Sanger sequencing. Sequence variants were classified and interpreted using the MITOMAP compendium of polymorphisms. 99.8% of the observed variations had been previously reported. The percentage of novel variants to POAG instances was 7-fold lower than a prior estimate. Novel mtDNA variants were present in 3 of 22 instances novel nonsynonymous changes in 1 of 22 instances and novel transversions in 0 of 22 instances; these proportions are significantly lower (p<.0005 p<.0004 p<.0001) than estimated previously for POAG and did not differ significantly from settings. Although it is possible that mitochondrial genetics play a role in African-Americans’ high susceptibility to POAG it is unlikely that any mitochondrial respiratory dysfunction is due to an abnormally high incidence of novel mutations that can be recognized in mtDNA from peripheral blood. Introduction Main open-angle glaucoma (POAG) is definitely defined as a spectrum of diseases causing vision loss as a result of progressive and irreversible retinal ganglion cell damage optic nerve degeneration and related visual field loss . African-Americans are disproportionately affected by POAG. A metaanalysis of 46 observational studies found that POAG prevalence in people over age 70 was 16% for blacks and 6% for whites  and the LDN193189 HCl age-adjusted prevalence rate of POAG in African-Americans is definitely four- to five-fold higher than whites . LDN193189 HCl Mitochondria are subcellular organelles descended from an ancient bacterial endosymbiont. They may be responsible for energy metabolism based on oxidative phosphorylation and play a central part in apoptosis and cells homeostasis. Although supported and controlled by ~1 500 nuclear genes human being mitochondria possess their personal genome mtDNA a circular molecule of 16 549 foundation pairs encoding 22 tRNAs 2 ribosomal RNAs and protein components of the electron transfer chain. mtDNA variants and haplogroups have been linked to neurodegenerative diseases including Parkinson’s LDN193189 HCl disease and Alzheimer’s disease . Mutations in mtDNA may result in degeneration of the optic nerve: a nonsynonymous mitochondrial mutation was first identified as the cause of Leber’s hereditary optic neuropathy (LHON) . Inheritance of Rabbit Polyclonal to Collagen XI alpha2. human being mtDNA is specifically maternal and all humans can trace their maternal ancestry back to a single African woman the most recent common ancestor (MRCA) who lived 194 300 +/- 32 550 LDN193189 HCl years ago . Sequence variants in mtDNA have accumulated in a manner proportional to divergence time providing rise to unique selections of ancestral variants “haplogroups” that reflect humanity’s African genesis and patterns of global migration. African mitochondrial haplogroups have been linked to elevated risk for POAG in Saudi individuals . Several lines of evidence suggest that mitochondrial genetics and function might play a role in POAG pathogenesis . For example a maternal family history of POAG is definitely more likely than a paternal one as would be expected from mitochondrial genetics: mothers LDN193189 HCl and sisters of glaucoma individuals were more likely to have glaucoma than fathers and brothers . The loss of retinal ganglion cells (RGC) is definitely characteristic of POAG and RGC have a high energy requirement which may make them especially vulnerable to mitochondrial dysfunction. A mitochondrial complex-I defect has been proposed like a mechanism for the loss of trabecular meshwork cells in POAG which were found to have higher levels of reactive oxygen species and to be more sensitive to mitochondrial inhibition than normal cells; treatment with antioxidants or mitochondrial permeability transition inhibitors might inhibit disease progression . Lymphocytes of POAG individuals were reported to have significantly lower mean mitochondrial respiratory activity and POAG lymphoblast cell lines were recently found to have a complex-I ATP synthesis defect [11-13]. Finally 52 of Saudi POAG instances were found to harbor novel potentially.