Nipradilol protects rat retinal ganglion cells from apoptosis induced by serum deprivation in vitro and by diabetes in vivo.
OBJECTIVE
To investigate if nipradilol has an anti-apoptotic effect in serum-deprived RGC-5 cells and in the streptozotocin-induced diabetic rat retina.


METHODS
Apoptosis was quantified by activated caspase-3 immunohistochemistry or terminal dUTP nick end-labeling assay.


RESULTS
Nipradilol dose-dependently suppressed apoptosis in a protein kinase A- and G-dependent manner and counteracted glutamate-induced calcium entry in the RGC-5 cells and reduced apoptotic cells in the retinal ganglion cell layer of 4- and 12-week diabetic retinas compared to controls when instilled for 5 days. Removal of the nitric oxide moiety from nipradilol blocked these effects.


CONCLUSIONS
Nipradilol protects RGCs from apoptosis induced by serum-deprivation in vitro and by diabetes in vivo. The NO-related signaling pathway mediates the anti-apoptotic ability of nipradilol.
Tatsumi
Yasuko
Y
Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan.
Kanamori
Akiyasu
A
Nagai-Kusuhara
Azusa
A
Nakanishi
Yoriko
Y
Agarwal
Neeraj
N
Negi
Akira
A
Nakamura
Makoto
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D008297:Male; D011412:Propanolamines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D044967:Serum; D014665:Vasodilator Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D011412:Propanolamines; D047428:Protein Kinase Inhibitors; D014665:Vasodilator Agents; D018698:Glutamic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; C036089:nipradilol; D002118:Calcium