title: Impaired complex-I-linked respiration and ATP synthesis in primary open-angle glaucoma patient lymphoblasts.
abstract: OBJECTIVE
  Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes of POAG patients, the authors sought to characterize mitochondrial function in a separate cohort of POAG.
  
  
  METHODS
  Using similar methodology to that previous applied to Leber's hereditary optic neuropathy (LHON) patients, maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well as cell growth rates in glucose and galactose media, were assessed in transformed lymphocytes from POAG patients (n = 15) and a group of age- and sex-matched controls (n = 15).
  
  
  RESULTS
  POAG lymphoblasts had significantly lower rates of complex-I-driven ATP synthesis, with preserved complex-II-driven ATP synthesis. Complex-I driven maximal respiration was also significantly decreased in patient cells. Growth in galactose media, where cells are forced to rely on mitochondrial ATP production, revealed no significant differences between the control and POAG cohort.
  
  
  CONCLUSIONS
  POAG lymphoblasts in the study cohort exhibited a defect in complex-I of the oxidative phosphorylation pathway, leading to decreased rates of respiration and ATP production. Studies in LHON and other diseases have established that lymphocyte oxidative phosphorylation measurement is a reliable indicator of systemic dysfunction of this pathway. While these defects did not impact lymphoblast growth when the cells were forced to rely on oxidative ATP supply, the authors suggest that in the presence of a multitude of cellular stressors as seen in the early stages of POAG, these defects may lead to a bioenergetic crisis in retinal ganglion cells and an increased susceptibility to cell death.
authors.affiliation: the    Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia, and the.
authors.forename: Shanjean
authors.initials: S
authors.lastname: Lee
authors.forename: Leo
authors.initials: L
authors.lastname: Sheck
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Crowston
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Van Bergen
authors.forename: Evelyn C
authors.initials: EC
authors.lastname: O'Neill
authors.forename: Fleur
authors.initials: F
authors.lastname: O'Hare
authors.forename: Yu Xiang George
authors.initials: YX
authors.lastname: Kong
authors.forename: Vicki
authors.initials: V
authors.lastname: Chrysostomou
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Vincent
authors.forename: Ian A
authors.initials: IA
authors.lastname: Trounce
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000368:Aged; D016022:Case-Control Studies; D019069:Cell Respiration; D042967:Electron Transport Complex I / Q000378:metabolism*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D042967:Electron Transport Complex I