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Constitutive Activation Mutant mTOR Promote Cone Survival in Retinitis Pigmentosa Mice

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1074))

Abstract

Studies form our laboratory and others show that the oncogenic tyrosine kinase and serine threonine kinase signaling pathways are essential for cone photoreceptor survival. These pathways are downregulated in mouse models of retinal degenerative diseases. In the present study, we found that activation mutants of mTOR delayed the death of cones in a mouse model of retinal degeneration. These studies suggest that oncogenic protein kinases may be useful as therapeutic agents to treat retinal degenerations that affect cones.

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References

  • Kim SG, Buel GR, Blenis J (2013) Nutrient regulation of the mTOR complex 1 signaling pathway. Mol Cells 73:4429–4438

    Google Scholar 

  • Mears AJ, Kondo M, Swain PK et al (2001) Nrl is required for rod photoreceptor development. Nat Genet 29:447–452

    Article  CAS  Google Scholar 

  • Punzo C, Cepko C (2007) Cellular responses to photoreceptor death in the rd1 mouse model of retinal degeneration. Invest Ophthalmol Vis Sci 48:849–857

    Article  Google Scholar 

  • Punzo C, Kornacker K, Cepko CL (2009) Stimulation of the insulin/mTOR pathway delays cone death in a mouse model of retinitis pigmentosa. Nat Neurosci 12:44–52

    Article  CAS  Google Scholar 

  • Rajala RV, Gardner TW (2016) Burning fat fuels photoreceptors. Nat Med 22:342–343

    Article  CAS  Google Scholar 

  • Rajala RV, McClellan ME, Ash JD et al (2002) In vivo regulation of phosphoinositide 3-kinase in retina through light-induced tyrosine phosphorylation of the insulin receptor beta-subunit. J Biol Chem 277:43319–43326

    Article  CAS  Google Scholar 

  • Rajala A, Anderson RE, Ma JX et al (2007) G-protein-coupled receptor rhodopsin regulates the phosphorylation of retinal insulin receptor. J Biol Chem 282:9865–9873

    Article  CAS  PubMed  Google Scholar 

  • Rajala A, Wang Y, Rajala RV (2016) Activation of oncogenic tyrosine kinase signaling promotes insulin receptor-mediated cone photoreceptor survival. Oncotarget 7:46924–46942

    Article  PubMed  PubMed Central  Google Scholar 

  • Reiling JH, Sabatini DM (2006) Stress and mTORture signaling. Oncogene 25:6373–6383

    Article  CAS  PubMed  Google Scholar 

  • Sabatini DM (2006) mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 6:729–734

    Article  CAS  PubMed  Google Scholar 

  • Sarbassov DD, Ali SM, Sabatini DM (2005) Growing roles for the mTOR pathway. Curr Opin Cell Biol 17:596–603

    Article  CAS  PubMed  Google Scholar 

  • Sato T, Nakashima A, Guo L et al (2010) Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer. Oncogene 29:2746–2752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmelzle T, Hall MN (2000) TOR, a central controller of cell growth. Cell 103:253–262

    Article  CAS  PubMed  Google Scholar 

  • Urano J, Sato T, Matsuo T et al (2007) Point mutations in TOR confer Rheb-independent growth in fission yeast and nutrient-independent mammalian TOR signaling in mammalian cells. Proc Natl Acad Sci U S A 104:3514–3519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Venkatesh A, Ma S, Le YZ et al (2015) Activated mTORC1 promotes long-term cone survival in retinitis pigmentosa mice. J Clin Invest 125:1446–1458

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Macke JP, Merbs SL et al (1992) A locus control region adjacent to the human red and green visual pigment genes. Neuron 9:429–440

    Article  CAS  PubMed  Google Scholar 

  • Warburg O (1956) On the origin of cancer cells. Science 123:309–314

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the National Institutes of Health (EY00871 and NEI Core grant EY021725) and an unrestricted grant from Research to Prevent Blindness, Inc., to the Department of Ophthalmology. The authors thank Dr. Claudio Punzo for providing us with the LacZ mice under the control of human red/green cone opsin promoter, which were generated in Dr. Jeremy Nathan’s laboratory at Johns Hopkins School of Medicine. The authors acknowledge Ms. Kathy J. Kyler, Staff Editor, University of Oklahoma Health Sciences Center, for editing this manuscript.

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Authors and Affiliations

  1. Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Ammaji Rajala, Yuhong Wang & Raju V. S. Rajala

  2. Dean McGee Eye Institute, Oklahoma City, OK, USA

    Ammaji Rajala & Yuhong Wang

  3. Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Raju V. S. Rajala

  4. Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Raju V. S. Rajala

  5. Dean McGee Eye Institute, Oklahoma City, OK, USA

    Raju V. S. Rajala

Authors
  1. Ammaji Rajala
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  2. Yuhong Wang
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  3. Raju V. S. Rajala
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Corresponding author

Correspondence to Raju V. S. Rajala .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. Ophthalmology and Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  3. School of Medicine Beckman Vision Center, University of California San Francisco, San Francisco, California, USA

    Matthew M. LaVail

  4. Departments of Ophthalmology and Cell Biology, Duke Eye Center, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

  5. Division of Ophthalmology, Case Western Reserve University, Cleveland, Ohio, USA

    Joe G. Hollyfield

  6. Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

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Rajala, A., Wang, Y., Rajala, R.V.S. (2018). Constitutive Activation Mutant mTOR Promote Cone Survival in Retinitis Pigmentosa Mice. In: Ash, J., Anderson, R., LaVail, M., Bowes Rickman, C., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1074. Springer, Cham. https://doi.org/10.1007/978-3-319-75402-4_61

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