Systemic propranolol reduces b-wave amplitude in the ERG and increases IGF-1 receptor phosphorylation in rat retina.
OBJECTIVE
To determine whether systemic application of propranolol, a nonselective beta-adrenergic receptor antagonist, with an osmotic pump will decrease the b-wave amplitude of the electroretinogram (ERG) and increase insulin-like growth factor (IGF)-1 receptor signaling.


METHODS
Young rats at 8 weeks of age were treated with saline, phentolamine, a nonselective alpha-adrenergic receptor antagonist, or propranolol, a nonselective beta-adrenergic receptor antagonist, delivered by osmotic pumps for 21 days. On the 21st day, all rats underwent electroretinographic analyses followed by collection of the retinas for protein assessment using Western blot analysis for IGF binding protein 3 (IGFBP3), IGF-1 receptor (IGF-1R), Akt, extracellular signal-related kinases 1 and 2 (ERK1/2), and vascular endothelial cell growth factor (VEGF).


RESULTS
Data indicate that 21 days of propranolol significantly decreased the b-wave amplitude of the ERG. The decrease in the b-wave amplitude occurred concurrently with a decrease in IGFBP3 levels and an increase in tyrosine phosphorylation of IGF-1 receptor on 1135/1136. This phosphorylation of IGF-1 receptor led to increased phosphorylation of Akt and ERK1/2. VEGF protein levels were also increased.


CONCLUSIONS
Overall, beta-adrenergic receptor antagonism produced a dysfunctional ERG, which occurred with an increase in IGF-1R phosphorylation and activation of VEGF. Systemic application of beta-adrenergic receptor antagonists may have detrimental effects on the retina.
Jiang
Youde
Y
Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Steinle
Jena J
JJ
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000818:Animals; D015153:Blotting, Western; D016503:Drug Delivery Systems; D004596:Electroretinography / Q000187:drug effects*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048053:Mitogen-Activated Protein Kinase 6 / Q000378:metabolism; D010766:Phosphorylation; D011433:Propranolol / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D018972:Insulin-Like Growth Factor Binding Protein 3; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D014443:Tyrosine; D011433:Propranolol; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6