The effect of 3-aminobenzamide, an inhibitor of poly-ADP-ribose polymerase, on ischemia/reperfusion damage in rat retina.
Excitotoxic amino acids, such as glutamate, may play an important role in retinal ischemia/reperfusion damage. In central neurons, excitotoxicity may be mediated by nitric oxide synthase (NOS) causing DNA damage via nitric oxide (NO). The nicked DNA activates poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) and may deplete intracellular ATP resulting in cell death. PARP may also be involved in apoptosis. We used 3-aminobenzamide (3-ABA), a PARP inhibitor, to examine the possible involvement of PARP in a rat model of retinal ischemia. Retinal ischemia was induced by elevating the intraocular pressure (IOP) through the insertion of a needle into the anterior chamber of a rat eye. IOP was raised to 110 mm Hg for 60 minutes. Animals were given intracameral infusion of 0, 1, 3, 10, 30, 100 mM 3-ABA in 0.1 M PBS, pH 7.4 during ischemia. Morphologic and morphometric evaluation at 7 days after reperfusion showed that 3-ABA at 3 mM and above significantly ameliorated the ischemic/reperfusion damage to the retina. In addition, at 10 mM 3-ABA inhibited the characteristic ladder pattern in DNA gel analysis seen in apoptosis of retinal neurons after ischemia/reperfusion. Hence, PARP may be involved in retinal cell loss after ischemia/reperfusion insult probably through the apoptotic pathway.
Lam
T T
TT
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago 60612, USA.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D053938:DNA Fragmentation / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006863:Hydrogen-Ion Concentration; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000188:drug therapy*; D012160:Retina / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
D001549:Benzamides; D004791:Enzyme Inhibitors; D009707:Nucleosomes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide