Mitochondrial decline precedes phenotype development in the complement factor H mouse model of retinal degeneration but can be corrected by near infrared light

Neurobiol Aging. 2015 Oct;36(10):2869-76. doi: 10.1016/j.neurobiolaging.2015.06.010. Epub 2015 Jun 15.

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.

Keywords: 670 nm; AMD; ATP; Aging; Retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Adenosine Triphosphate / physiology
  • Animals
  • Brain / metabolism
  • Chaperonin 60 / metabolism
  • Complement Factor H* / genetics
  • Disease Models, Animal
  • Inflammation / radiotherapy
  • Infrared Rays / therapeutic use*
  • Macular Degeneration / genetics*
  • Macular Degeneration / pathology
  • Macular Degeneration / radiotherapy*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Photoreceptor Cells, Vertebrate / pathology
  • Photoreceptor Cells, Vertebrate / radiation effects
  • Retina / metabolism*

Substances

  • Chaperonin 60
  • Complement Factor H
  • Adenosine Triphosphate