Effects of poly(ADP-ribose) polymerase inhibitor on NMDA-induced retinal injury.
OBJECTIVE
Excessive activation of poly(ADP-ribose) polymerase (PARP), a nuclear enzyme that is activated by DNA damage, leads to neuronal cell death through depletion of ATP. The purpose of this study was to determine whether inhibition of PARP has some neuroprotective effects on the N-methyl-D-aspartate (NMDA)-induced functional and morphological injury to the rabbit retina.


METHODS
Visually evoked potentials (VEPs) were recorded at different times after an intravitreal injection of NMDA (200, 660, and 2000 nmol) alone, or NMDA with 3-aminobenzamide (ABA, 200 nmol), a PARP inhibitor, or with MK-801 (200 nmol), an NMDA antagonist. The physiological changes were followed for 2 weeks, after which the eyes were enuculeated and prepared for histological examinations.


RESULTS
Intravitreal injections of NMDA reduced the amplitudes of rabbit VEPs and the number of cells in the retinal ganglion cell layer in a dose-dependent manner. No significant changes could be detected in the bright-flash electroretinograms (ERGs). Simultaneous injection of MK-801 (200 nmol) significantly diminished the changes induced by intravitreal NMDA. 3-Aminobenzamide (ABA) (200 nmol) also suppressed these changes, but its effects were less than those of MK-801.


CONCLUSIONS
NMDA-induced retinal damage can be detected by VEPs, and PARP inhibition has some neuroprotective effects on the NMDA-induced retinal damage.
Oku
Hidehiro
H
Department of Ophthalmology, Osaka Medical College, Osaka, Japan. hidehirooku@aol.com
Goto
Wakana
W
Okuno
Takashi
T
Kobayashi
Takatoshi
T
Sugiyama
Tetsuya
T
Ota
Takashi
T
Yoneda
Shinji
S
Hara
Hideaki
H
Ikeda
Tsunehiko
T
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002452:Cell Count; D019610:Cytoprotection; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005074:Evoked Potentials, Visual; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007267:Injections; D016202:N-Methylaspartate / Q000633:toxicity*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology; D012164:Retinal Diseases / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology; D014822:Vitreous Body
D001549:Benzamides; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases