title: Glycolysis in patients with age-related macular degeneration.
abstract: OBJECTIVE
  Retinal adenosine triphosphate is mainly produced via glycolysis, so inhibition of glycolysis may promote the onset and progression of age-related macular degeneration (AMD). When glycolysis is inhibited, pyruvate is metabolized by lactic acid fermentation instead of entering the mitochondrial tricarboxylic acid (TCA) cycle. We measured urinary pyruvate and lactate levels in patients with AMD.
  
  
  METHODS
  Eight patients with typical AMD (tAMD group) and 9 patients with polypoidal choroidal vasculopathy (PCV group) were enrolled. Urinary levels of pyruvate, lactate, α-hydroxybutyrate, and β-hydroxybutyrate were measured in all patients.
  
  
  RESULTS
  The mean urinary levels of pyruvate and lactate were 8.0 ± 2.8 and 7.5 ± 8.3 μg/mg creatinine (reference values: 0.5-6.6 and 0.0-1.6), respectively, with the mean increase over the reference value being 83.6 ± 51.1% and 426.5 ± 527.8%, respectively. In 12 patients (70.6%), the lactate/pyruvate ratio was above the reference range. Urinary levels of α-hydroxybutyrate and β-hydroxybutyrate were decreased by -31.9 ± 15.2% and -33.1 ± 17.5% compared with the mean reference values. There were no significant differences of any of these glycolysis metabolites between the tAMD and PCV groups. Multivariate analysis revealed that none of the variables tested, including patient background factors (age, hypertension, diabetes, hyperlipidemia, cerebrovascular disease, alcohol, smoking, visual acuity, and AMD phenotype), were significantly associated with the lactate/pyruvate ratio.
  
  
  CONCLUSIONS
  A high lactate/pyruvate ratio is a well-known marker of mitochondrial impairment, and it indicates poor oxidative function in AMD. Our results suggest that increased lactate levels may be implicated in the pathogenesis of AMD.
authors.affiliation: Department of Ophthalmology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Yokosako
authors.affiliation: Department of Ophthalmology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Mimura
authors.affiliation: Department of Ophthalmology, Yachiyo Medical Center, Tokyo Women's Medical University, Chiba, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Funatsu
authors.affiliation: Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Noma
authors.affiliation: Department of Ophthalmology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Ophthalmology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kamei
authors.affiliation: Department of Ophthalmology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Department of Ophthalmology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Matsubara
keywords: Age-related macular degeneration; glycolysis; ketone body; lactate; pyruvate.