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Role of Sirtuins in Retinal Function Under Basal Conditions

  • Jonathan B. Lin
  • Shunsuke Kubota
  • Raul Mostoslavsky
  • Rajendra S. ApteEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1074)

Abstract

Sirtuins are NAD+-dependent enzymes that govern cellular homeostasis by regulating the acylation status of their diverse target proteins. We recently demonstrated that both rod and cone photoreceptors rely on NAMPT-mediated NAD+ biosynthesis to meet their energetic requirements. Moreover, we found that this NAD+-dependent retinal homeostasis relies, in part, on maintenance of optimal activity of the mitochondrial sirtuins and of SIRT3 in particular. Nonetheless, it is unknown whether other sirtuin family members also play important roles in retinal homeostasis. Our results suggest that SIRT1, SIRT2, SIRT4, and SIRT6 are dispensable for retinal survival at baseline, as individual deletion of each of these sirtuins does not cause retinal degeneration by fundus biomicroscopy or retinal dysfunction by ERG. These findings have significant implications and inform future studies investigating the mechanisms underlying the central role of NAD+ biosynthesis in retinal survival and function.

Keywords

Sirtuins NAD+ Retinal degeneration Neurodegeneration Photoreceptors Retina 

Notes

Acknowledgments

This work was supported by NIH Grants R01 EY019287 (R.S.A.) and P30 EY02687 (Vision Core Grant); the C.M. and M.A. Reeves Foundation (R.S.A.); Research to Prevent Blindness (R.S.A.); the Hope Center (R.S.A.); the Lacy Foundation (S.K.); the Schulak Family Gift Fund for Retinal Research (R.S.A.); the Jeffrey Fort Innovation Fund (R.S.A.); and the Robert Machemer Foundation (S.K.). Additional funding comes from an unrestricted grant to the Department of Ophthalmology and Visual Sciences of Washington University School of Medicine from Research to Prevent Blindness. J.B.L. was supported by the Washington University in St. Louis Medical Scientist Training Program (NIH Grant T32 GM007200), the Washington University in St. Louis Institute of Clinical and Translational Sciences (NIH Grants UL1 TR000448, TL1 TR000449), the Washington University Diabetic Cardiovascular Disease Center, the American Federation for Aging Research, and the VitreoRetinal Surgery Foundation.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Jonathan B. Lin
    • 1
    • 2
  • Shunsuke Kubota
    • 1
  • Raul Mostoslavsky
    • 3
  • Rajendra S. Apte
    • 1
    • 4
    • 5
    Email author
  1. 1.Department of Ophthalmology & Visual SciencesWashington University School of MedicineSt. LouisUSA
  2. 2.Neuroscience Graduate Program, Division of Biology and Biomedical SciencesWashington University School of MedicineSt. LouisUSA
  3. 3.Massachusetts General Hospital Cancer Center, Harvard Medical SchoolBostonUSA
  4. 4.Department of Developmental BiologyWashington University School of MedicineSt. LouisUSA
  5. 5.Department of MedicineWashington University School of MedicineSt. LouisUSA

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