title: High glucose induces mitochondrial morphology and metabolic changes in retinal pericytes.
abstract: OBJECTIVE
  Mitochondrial dysfunction is known to play a role in retinal vascular cell loss, a prominent lesion of diabetic retinopathy. High glucose (HG) has been reported to induce mitochondrial fragmentation and dysfunction in retinal endothelial cells, contributing to apoptosis. In this study, the effects of HG on mitochondrial morphology, membrane potential, and metabolic changes and whether they could contribute to HG-induced apoptosis in retinal pericytes were investigated.
  
  
  METHODS
  Bovine retinal pericytes (BRPs) were grown in normal or HG medium for 7 days. Both sets of cells were double stained with mitochondrial membrane potential-independent dye and tetramethylrhodamine-ethyl-ester-perchlorate (TMRE) and imaged by confocal microscopy. The images were analyzed for average mitochondria shape, by using form factor and aspect ratio values, and membrane potential changes, by using the ratio between the red and green dye. BRPs grown in normal or HG medium were analyzed for transient changes in oxygen consumption and extracellular acidification with a flux analyzer and apoptosis by TUNEL assay.
  
  
  RESULTS
  BRPs grown in HG media exhibited significant fragmentation of mitochondria and increased membrane potential heterogeneity compared with the BRPs grown in normal medium. Concomitantly, BRPs grown in HG showed reduced steady state and maximum oxygen consumption and reduced extracellular acidification. Number of TUNEL-positive pericytes was increased in HG condition as well.
  
  
  CONCLUSIONS
  In HG condition, mitochondria of retinal pericytes display significant fragmentation, metabolic dysfunction, and reduced extracellular acidification. The detrimental effects of HG on mitochondrial function and cellular metabolism could play a role in the accelerated apoptosis associated with the retinal pericytes in diabetic retinopathy.
authors: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors: Kyle
authors: K
authors: Trudeau
authors: Anthony J A
authors: AJ
authors: Molina
authors: Sayon
authors: S
authors: Roy
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000166:cytology*
chemical_list: D000143:Acids; D005947:Glucose