title: To unite or divide: mitochondrial dynamics in the murine outer retina that preceded age related photoreceptor loss.
abstract: Mitochondrial function declines with age and is associated with age-related disorders and cell death. In the retina this is critical as photoreceptor energy demands are the greatest in the body and aged cell loss large (~30%). But mitochondria can fuse or divide to accommodate changing demands. We explore ageing mitochondrial dynamics in young (1 month) and old (12 months) mouse retina, investigating changes in mitochondrial fission (Fis1) and fusion (Opa1) proteins, cytochrome C oxidase (COX III), which reflects mitochondrial metabolic status, and heat shock protein 60 (Hsp60) that is a mitochondrial chaperon for protein folding.Western blots showed each protein declined with age. However, within this, immunostaining revealed increases of around 50% in Fis1 and Opa1 in photoreceptor inner segments (IS). Electron microscope analysis revealed mitochondrial fragmentation with age and marked changes in morphology in IS, consistent with elevated dynamics. COX III declined by approximately 30% in IS, but Hsp60 reductions were around 80% in the outer plexiform layer.Our results are consistent with declining mitochondrial metabolism. But also with increased photoreceptor mitochondrial dynamics that differ from other retinal regions, perhaps reflecting attempts to maintain function. These changes are the platform for age related photoreceptor loss initiated after 12 months.
authors.affiliation: Institute of Ophthalmology, University College London, London, UK.
authors.forename: Jaimie Hoh
authors.initials: JH
authors.lastname: Kam
authors.affiliation: Institute of Ophthalmology, University College London, London, UK.
authors.forename: Glen
authors.initials: G
authors.lastname: Jeffery
mesh_terms: D000375:Aging; D000818:Animals; D018834:Chaperonin 60 / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010786:Photoreceptor Cells / Q000378:metabolism*; D017510:Protein Folding; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D012164:Retinal Diseases / Q000378:metabolism*; D055211:Retinal Photoreceptor Cell Inner Segment / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018834:Chaperonin 60; C561064:FIS1 protein, mouse; D024101:Mitochondrial Proteins; D003576:Electron Transport Complex IV; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse
keywords: Gerotarget; ageing; fission; fusion; mitochondria