Prevention of chloroquine-induced electroretinographic damage by a new platelet-activating factor antagonist, BN 50730.
Chloroquine retinopathy is a severe toxic retinal impairment which may result in loss of vision by alterations of the retinal pigment epithelium and photoreceptors. Currently, there is no specific treatment for this retinopathy. Platelet-activating factor (PAF) is known to modulate retinal function and is one of the major immunomediators of the retina. In order to test the possible involvement of PAF in chloroquine-induced retinopathy and the effectiveness of PAF antagonists in the prevention of this condition, we investigated the effects of BN 50730, a specific PAF antagonist, on the electroretinogram (ERG) of the isolated rat retina exposed to chloroquine. When retinas from normal rats were perfused with chloroquine (10(-6) M), a marked and rapid decrease in b-wave amplitude was observed. In contrast, chloroquine had no effect on the b-wave of the retina isolated from animals pretreated with the PAF antagonist BN 50730 (30 mg/kg/day, i.p., for 5 days). The results obtained indicate that (i) chloroquine is a toxic drug for retinal function, (ii) PAF plays a key role in the mediation of chloroquine retinopathy and (iii) PAF antagonists may constitute valuable agents for the treatment of this retinal impairment.
Doly
M
M
Laboratoire de Biophysique, INSERM U71, Facultés de Médecine et de Pharmacie, Clermont-Ferrand, France.
Cluzel
J
J
Millerin
M
M
Bonhomme
B
B
Braquet
P
P
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002738:Chloroquine; D003623:Dark Adaptation; D004596:Electroretinography / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000502:physiology; D012164:Retinal Diseases / Q000139:chemically induced / Q000503:physiopathology*; D013777:Tetrazoles / Q000494:pharmacology*; D058924:Thienopyridines; D014230:Triazoles
D001381:Azepines; D010972:Platelet Activating Factor; D013777:Tetrazoles; D058924:Thienopyridines; D014230:Triazoles; C066686:BN 50730; D002738:Chloroquine