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2018 Mar-Apr;5 (2):

Photoreceptor Protection by Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF).

Jianmin Lu, Lingyu Luo, Deqiang Huang, Xian Liu, Xin Xia, Zhengying Wang, Byron L Lam, Jinglin Yi, Rong Wen, Yiwen Li
Author Information
  1. Jianmin Lu: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL 33136.
  2. Lingyu Luo: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL 33136.
  3. Deqiang Huang: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL 33136.
  4. Xian Liu: Eye Hospital, Nanchang University, Jiangxi Medical School, Nanchang, 330006, China.
  5. Xin Xia: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL 33136.
  6. Zhengying Wang: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL 33136.
  7. Byron L Lam: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL 33136.
  8. Jinglin Yi: Eye Hospital, Nanchang University, Jiangxi Medical School, Nanchang, 330006, China.
  9. Rong Wen: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL 33136.
  10. Yiwen Li: Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL 33136.
PMID: 29687079 DOI: 10.1523/ENEURO.0109-18.2018

Abstract

Retinal degenerations are a major cause of vision impairment and blindness. Neuroprotective therapy is a promising therapeutic strategy for retinal degenerative diseases. We investigated a novel neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) in the retina. MANF is expressed at a high level during postnatal development and the expression declines to a lower level as the retina matures. Müller cells are the major cells expressing MANF. It is also found in the retinal ganglion cells, in the inner nuclear layer (INL) neurons, and in retinal pigment epithelial (RPE) cells. Intravitreal injection of recombinant human (rh)MANF significantly protected rod and cone photoreceptors in rats carrying the rhodopsin S334ter mutation, and preserved electroretinograms (ERGs) in the ( ) mice. These results indicate that MANF is a native protein in the retina and is a potent neurotrophic factor for photoreceptor protection.

Keywords

MANF RGC degeneration neuroprotection photoreceptor retina

References

  1. PLoS One. 2011 Mar 30;6(3):e18282 [PMID: 21479182]
  2. Mol Ther. 2011 Feb;19(2):234-42 [PMID: 21139570]
  3. Nature. 2007 Jul 5;448(7149):73-7 [PMID: 17611540]
  4. Vision Res. 2007 Mar;47(5):624-33 [PMID: 17267005]
  5. Eur J Pharmacol. 2015 Mar 5;750:118-22 [PMID: 25637781]
  6. Cell Death Dis. 2015 Dec 31;6:e2032 [PMID: 26720341]
  7. Vision Res. 2002 Feb;42(4):517-25 [PMID: 11853768]
  8. Am J Ophthalmol. 2013 Aug;156(2):283-292.e1 [PMID: 23668681]
  9. Am J Ophthalmol. 2015 Apr;159(4):659-666.e1 [PMID: 25528956]
  10. Mol Cell Neurosci. 2008 Nov;39(3):356-71 [PMID: 18718866]
  11. Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3896-901 [PMID: 16505355]
  12. Neuron. 2014 Jan 22;81(2):349-65 [PMID: 24462098]
  13. Sci Rep. 2016 Mar 10;6:22632 [PMID: 26961159]
  14. Invest Ophthalmol Vis Sci. 2003 Sep;44(9):4069-75 [PMID: 12939330]
  15. Retina. 2018 Jan;38 Suppl 1:S27-S32 [PMID: 28541963]
  16. J Comp Neurol. 2009 Jul 1;515(1):116-24 [PMID: 19399876]
  17. N Engl J Med. 2015 May 14;372(20):1887-97 [PMID: 25938638]
  18. Exp Eye Res. 1975 Aug;21(2):167-92 [PMID: 1164921]
  19. Invest Ophthalmol Vis Sci. 2008 May;49(5):2148-55 [PMID: 18436848]
  20. N Engl J Med. 2008 May 22;358(21):2231-9 [PMID: 18441371]
  21. J Biol Chem. 2011 Jan 28;286(4):2675-80 [PMID: 21047780]
  22. Science. 2016 Jul 1;353(6294):aaf3646 [PMID: 27365452]
  23. Hum Gene Ther. 2008 Oct;19(10):979-90 [PMID: 18774912]
  24. N Engl J Med. 2015 May 14;372(20):1920-6 [PMID: 25936984]
  25. FEBS Lett. 2015 Dec 21;589(24 Pt A):3739-48 [PMID: 26450777]
  26. J Mol Neurosci. 1998 Dec;11(3):209-21 [PMID: 10344791]
  27. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):E517-25 [PMID: 23341635]
  28. Invest Ophthalmol Vis Sci. 2011 Apr 06;52(5):2219-26 [PMID: 21087953]
  29. J Biol Chem. 2013 Feb 8;288(6):4209-25 [PMID: 23255601]
  30. Lancet. 2006 Nov 18;368(9549):1795-809 [PMID: 17113430]
  31. Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4278-83 [PMID: 18586879]
  32. J Neurochem. 2012 Sep;122(5):1047-53 [PMID: 22726126]
  33. Hum Genet. 2015 Sep;134(9):967-80 [PMID: 26077850]
  34. Dev Neurobiol. 2010 Apr;70(5):360-71 [PMID: 20186704]
  35. J Neurosci. 1999 Jun 15;19(12):4778-85 [PMID: 10366612]
  36. Prog Retin Eye Res. 2012 Mar;31(2):136-51 [PMID: 22182585]
  37. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6241-5 [PMID: 21444807]
  38. J Neurosci. 2009 Jul 29;29(30):9651-9 [PMID: 19641128]
  39. Curr Eye Res. 2017 Mar;42(3):334-347 [PMID: 28362177]
  40. PLoS One. 2014 Feb 28;9(2):e90433 [PMID: 24587361]
  41. J Comp Neurol. 1986 Jul 22;249(4):499-510, 482-3 [PMID: 3745505]
  42. Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3292-8 [PMID: 12356837]
  43. J Comp Neurol. 1983 Nov 20;221(1):31-41 [PMID: 6643744]
  44. J Neurosci. 2006 Dec 27;26(52):13523-30 [PMID: 17192435]
  45. N Engl J Med. 2008 May 22;358(21):2240-8 [PMID: 18441370]
  46. Am J Ophthalmol. 2016 Oct;170:10-14 [PMID: 27457255]
  47. J Mol Neurosci. 2003 Apr;20(2):173-88 [PMID: 12794311]
  48. PLoS One. 2010 Mar 02;5(3):e9495 [PMID: 20209167]
  49. Neurobiol Dis. 2017 Jan;97(Pt B):90-102 [PMID: 27425895]
  50. Protein Eng Des Sel. 2009 Apr;22(4):233-41 [PMID: 19258449]
  51. Cell Rep. 2014 Apr 24;7(2):366-75 [PMID: 24726366]

Grants

  1. R01 EY015289/NEI NIH HHS
  2. R01 EY018586/NEI NIH HHS
  3. P30 EY002162/NEI NIH HHS
  4. P30 EY014801/NEI NIH HHS

MeSH Term

Animals
Disease Models, Animal
Electroretinography
Female
Humans
Intravitreal Injections
Male
Mice
Mice, Transgenic
Nerve Growth Factors
Neuroprotective Agents
Rats
Rats, Sprague-Dawley
Rats, Transgenic
Recombinant Proteins
Retinal Cone Photoreceptor Cells
Retinal Degeneration
Retinal Rod Photoreceptor Cells

Chemicals

MANF protein, human
Nerve Growth Factors
Neuroprotective Agents
Recombinant Proteins
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 19

Word Cloud

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