title: Mitochondrial decline precedes phenotype development in the complement factor H mouse model of retinal degeneration but can be corrected by near infrared light.
abstract: Mitochondria produce adenosine triphosphate (ATP), critical for cellular metabolism. ATP declines with age, which is associated with inflammation. Here, we measure retinal and brain ATP in normal C57BL/6 and complement factor H knockout mice (Cfh(-/-)), which are proposed as a model of age-related macular degeneration. We show a significant premature 30% decline in retinal ATP in Cfh(-/-) mice and a subsequent shift in expression of a heat shock protein that is predominantly mitochondrial (Hsp60). Changes in Hsp60 are associated with stress and neuroprotection. We find no differences in brain ATP between C57BL/6 and Cfh(-/-) mice. Near infrared (NIR) increases ATP and reduces inflammation. ATP decline in Cfh(-/-) mice was corrected with NIR which also shifted Hsp60 labeling patterns. ATP decline in Cfh(-/-) mice occurs before inflammation becomes established and photoreceptor loss occurs and may relate to disease etiology. However, ATP levels were corrected with NIR. In summary, we provide evidence for a mitochondrial basis for this disease in mice and correct this with simple light exposure known to improve mitochondrial function.
authors.affiliation: Program of Neurosciences, Institute of Biology, Federal Fluminense University, Rio de Janeiro, Brazil; Institute of Ophthalmology University College London, London, UK.
authors.forename: Karin C
authors.initials: KC
authors.lastname: Calaza
authors.affiliation: Institute of Ophthalmology University College London, London, UK.
authors.forename: Jaimie Hoh
authors.initials: JH
authors.lastname: Kam
authors.affiliation: Moorfields Eye Hospital, London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Hogg
authors.affiliation: Institute of Ophthalmology University College London, London, UK. Electronic address: g.jeffery@ucl.ac.uk.
authors.forename: Glen
authors.initials: G
authors.lastname: Jeffery
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism; D018834:Chaperonin 60 / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics; D004195:Disease Models, Animal; D007249:Inflammation / Q000532:radiotherapy; D007259:Infrared Rays / Q000627:therapeutic use*; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology / Q000528:radiation effects; D012160:Retina / Q000378:metabolism*
chemical_list: D018834:Chaperonin 60; D017242:Complement Factor H; D000255:Adenosine Triphosphate
keywords: 670 nm; AMD; ATP; Aging; Retina