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Cammalleri M, Locri F, Catalani E, et al. The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy. Front Cell Neurosci. 2017;11:395doi: 10.3389/fncel.2017.00395.
Cammalleri, M., Locri, F., Catalani, E., Filippi, L., Cervia, D., Dal Monte, M., & Bagnoli, P. (2017). The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy. Frontiers in cellular neuroscience, 11395. https://doi.org/10.3389/fncel.2017.00395
Cammalleri, Maurizio, et al. "The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy." Frontiers in cellular neuroscience vol. 11 (2017): 395. doi: https://doi.org/10.3389/fncel.2017.00395
Cammalleri M, Locri F, Catalani E, Filippi L, Cervia D, Dal Monte M, Bagnoli P. The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy. Front Cell Neurosci. 2017 Dec 12;11:395. doi: 10.3389/fncel.2017.00395. eCollection 2017. PMID: 29375312; PMCID: PMC5770647.
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Front Cell Neurosci. 2017 Dec 12;11:395. doi: 10.3389/fncel.2017.00395. eCollection 2017.

The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy.

Frontiers in cellular neuroscience

Maurizio Cammalleri, Filippo Locri, Elisabetta Catalani, Luca Filippi, Davide Cervia, Massimo Dal Monte, Paola Bagnoli

Affiliations

  1. Department of Biology, University of Pisa, Pisa, Italy.
  2. Department for Innovation in Biological, Agro-Food and Forest Systems, University of Tuscia, Viterbo, Italy.
  3. Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, Meyer University Children's Hospital, Florence, Italy.

PMID: 29375312 PMCID: PMC5770647 DOI: 10.3389/fncel.2017.00395

Abstract

In a mouse model of oxygen induced retinopathy (OIR), beta adrenergic receptor (BAR) blockade has been shown to recover hypoxia-associated retinal damages. Although the adrenergic signaling is an important regulator of apoptotic and autophagic processes, the role of BARs in retinal cell death remains to be elucidated. The present study was aimed at investigating whether ameliorative effects of BAR blockers may occur through their coordinated action on apoptosis and autophagy. To this aim, retinas from control and OIR mice untreated or treated with propranolol, a non-selective BAR1/2 blocker, were characterized in terms of expression and localization of apoptosis and autophagy markers. The effects of propranolol on autophagy signaling were also evaluated and specific autophagy modulators were used to get functional information on the autophagic effects of BAR antagonism. Finally, propranolol effects on neurodegenerative processes were associated to an electrophysiological investigation of retinal function by recording electroretinogram (ERG). We found that retinas of OIR mice are characterized by increased apoptosis and decreased autophagy, while propranolol reduces apoptosis and stimulates autophagy. In particular, propranolol triggers autophagosome formation in bipolar, amacrine and ganglion cells that are committed to die by apoptosis in response to hypoxia. Also our data argue that propranolol, through the inhibition of the Akt-mammalian target of rapamycin pathway, activates autophagy which decreases retinal cell death. At the functional level, propranolol recovers dysfunctional ERG by recovering the amplitude of a- and b-waves, and oscillatory potentials, thus indicating an efficient restoring of retinal transduction. Overall, our results demonstrate that BAR1/2 are key regulators of retinal apoptosis/autophagy, and that BAR1/2 blockade leads to autophagy-mediated neuroprotection. Reinstating the balance between apoptotic and autophagic machines may therefore be viewed as a future goal in the treatment of retinopathies.

Keywords: apoptosis; autophagy; beta adrenergic receptors; electroretinogram; proliferative retinopathies; propranolol; retinal neurons

References

  1. Invest Ophthalmol Vis Sci. 2010 May;51(5):2730-5 - PubMed
  2. Cell Death Dis. 2011 Apr 14;2:e144 - PubMed
  3. Naunyn Schmiedebergs Arch Pharmacol. 2003 Jun;367(6):578-87 - PubMed
  4. Curr Opin Pharmacol. 2013 Feb;13(1):72-7 - PubMed
  5. J Perinat Med. 2016 Jul 1;44(5):499-503 - PubMed
  6. Prog Retin Eye Res. 2014 Sep;42:103-29 - PubMed
  7. Autophagy. 2015;11(6):939-53 - PubMed
  8. Invest Ophthalmol Vis Sci. 2011 Jan 05;52(1):155-70 - PubMed
  9. PLoS One. 2011;6(7):e22460 - PubMed
  10. Neuroreport. 2011 Sep 14;22(13):633-6 - PubMed
  11. Mol Cell Biol. 2005 Feb;25(3):1025-40 - PubMed
  12. Autophagy. 2011 Jun;7(6):643-4 - PubMed
  13. JAMA Ophthalmol. 2013 Mar;131(3):376-82 - PubMed
  14. Invest Ophthalmol Vis Sci. 2010 Jun;51(6):2813-26 - PubMed
  15. Oncotarget. 2015 May 10;6(13):11264-80 - PubMed
  16. Eur J Pharmacol. 2008 Jul 28;589(1-3):14-21 - PubMed
  17. Invest Ophthalmol Vis Sci. 1994 Jan;35(1):101-11 - PubMed
  18. Cardiovasc Res. 2009 Jun 1;82(3):439-47 - PubMed
  19. Mol Med Rep. 2015 Oct;12 (4):4887-94 - PubMed
  20. Naunyn Schmiedebergs Arch Pharmacol. 2002 Mar;365(3):200-9 - PubMed
  21. Pharmacol Res. 2017 Sep 29;:null - PubMed
  22. J Neurosci. 2002 May 15;22(10):3987-93 - PubMed
  23. Autophagy. 2014;10(11):1989-2005 - PubMed
  24. Front Cell Neurosci. 2016 Feb 19;10:42 - PubMed
  25. Skelet Muscle. 2014 Dec 12;4(1):22 - PubMed
  26. J Mol Med (Berl). 2013 Dec;91(12):1407-19 - PubMed
  27. J Comp Neurol. 2011 Feb 15;519(3):506-27 - PubMed
  28. Adv Exp Med Biol. 2012;723:83-90 - PubMed
  29. Int J Clin Exp Med. 2015 Aug 15;8(8):12252-63 - PubMed
  30. Eur J Neurosci. 2007 Mar;25(5):1447-59 - PubMed
  31. J Comp Neurol. 2000 Aug 14;424(1):1-23 - PubMed
  32. Invest Ophthalmol Vis Sci. 2016 Aug 1;57(10 ):4356-66 - PubMed
  33. Exp Eye Res. 2013 Jun;111:27-35 - PubMed
  34. Exp Eye Res. 2014 Jul;124:56-66 - PubMed
  35. PLoS One. 2016 Jan 15;11(1):e0146517 - PubMed
  36. Pediatr Blood Cancer. 2015 Aug;62(8):1414-20 - PubMed
  37. Autophagy. 2016;12 (1):1-222 - PubMed
  38. J Neurochem. 2008 Sep;106(5):2224-35 - PubMed
  39. Int J Ophthalmol. 2016 Jun 18;9(6):821-4 - PubMed
  40. Prog Retin Eye Res. 1998 Oct;17(4):485-521 - PubMed
  41. BMC Pediatr. 2017 Jul 14;17 (1):165 - PubMed
  42. Autophagy. 2010 Oct;6(7):922-8 - PubMed
  43. Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8228-35 - PubMed
  44. Invest Ophthalmol Vis Sci. 2012 Apr 24;53(4):2181-92 - PubMed
  45. J Physiol. 2003 Mar 1;547(Pt 2):509-30 - PubMed
  46. Autophagy. 2013 Jul;9(7):973-84 - PubMed
  47. J Clin Invest. 2015 Jan;125(1):5-13 - PubMed
  48. Pancreas. 2009 Jan;38(1):94-100 - PubMed
  49. Exp Eye Res. 2015 Aug;137:84-93 - PubMed
  50. Histol Histopathol. 2016 May;31(5):479-98 - PubMed
  51. Prog Retin Eye Res. 2016 Nov;55:206-245 - PubMed
  52. Cell. 2009 Jun 12;137(6):1001-4 - PubMed
  53. Exp Cell Res. 2014 Jan 15;320(2):269-80 - PubMed
  54. Biochim Biophys Acta. 2009 Sep;1793(9):1485-95 - PubMed
  55. Cell Tissue Res. 2009 Jun;336(3):423-38 - PubMed
  56. Int J Dev Biol. 2004;48(8-9):965-74 - PubMed
  57. Arch Dis Child. 2013 Jul;98(7):565-7 - PubMed
  58. Trends Endocrinol Metab. 2014 May;25(5):274-82 - PubMed
  59. Invest Ophthalmol Vis Sci. 2011 May 05;52(6):2967-75 - PubMed
  60. J Neurochem. 2012 Mar;120(5):818-29 - PubMed
  61. Curr Drug Targets. 2014;15(10):956-64 - PubMed
  62. Diabetologia. 2016 Oct;59(10 ):2251-61 - PubMed
  63. Endocrinology. 2003 Aug;144(8):3344-50 - PubMed
  64. J Pediatr. 2013 Dec;163(6):1570-1577.e6 - PubMed
  65. Rejuvenation Res. 2008 Feb;11(1):215-26 - PubMed
  66. Curr Opin Ophthalmol. 2014 May;25(3):228-33 - PubMed
  67. J Neurochem. 2011 Dec;119(6):1317-29 - PubMed
  68. Apoptosis. 2007 Aug;12(8):1349-63 - PubMed
  69. Sci Rep. 2016 Feb 05;6:20639 - PubMed
  70. Br J Pharmacol. 2010 Jul;160(5):1048-61 - PubMed
  71. Mol Neurodegener. 2015 Aug 26;10 :40 - PubMed
  72. Arch Ophthalmol. 1987 Jul;105(7):929-33 - PubMed
  73. Biol Pharm Bull. 2015;38(2):321-4 - PubMed
  74. J Pediatr Surg. 2012 Dec;47(12):2216-23 - PubMed
  75. Invest Ophthalmol Vis Sci. 2014 Dec 11;56(1):59-73 - PubMed
  76. Int J Biol Sci. 2016 Oct 25;12 (11):1332-1340 - PubMed
  77. Cell Death Differ. 2012 Jan;19(1):162-9 - PubMed
  78. Prog Retin Eye Res. 2009 Nov;28(6):452-82 - PubMed
  79. Curr Neuropharmacol. 2016;14 (8):810-825 - PubMed
  80. Cell Death Differ. 2015 Mar;22(3):476-87 - PubMed
  81. Exp Eye Res. 2010 Aug;91(2):171-9 - PubMed
  82. Exp Eye Res. 2015 Jun;135:67-80 - PubMed
  83. J Comp Neurol. 2000 Aug 21;424(2):327-38 - PubMed
  84. J Neurobiol. 1991 Jan;22(1):85-96 - PubMed
  85. Oncotarget. 2016 May 3;7(18):24995-5009 - PubMed
  86. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2392-407 - PubMed
  87. Mol Pharmacol. 2014 Nov;86(5):479-84 - PubMed
  88. Naunyn Schmiedebergs Arch Pharmacol. 2012 May;385(5):481-94 - PubMed

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