Doly M, Cluzel J, Millerin M, Bonhomme B, Braquet P
Laboratoire de Biophysique, INSERM U71, Facultés de Médecine et de Pharmacie, Clermont-Ferrand, France.
Ophthalmic Res. 1993;25(5):314-8. doi: 10.1159/000267331.
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.
氯喹视网膜病变是一种严重的中毒性视网膜损害，可通过视网膜色素上皮和光感受器的改变导致视力丧失。目前，对于这种视网膜病变尚无特异性治疗方法。已知血小板活化因子（PAF）可调节视网膜功能，并且是视网膜的主要免疫介质之一。为了测试PAF在氯喹诱导的视网膜病变中的可能作用以及PAF拮抗剂在预防这种情况方面的有效性，我们研究了特异性PAF拮抗剂BN 50730对暴露于氯喹的离体大鼠视网膜电图（ERG）的影响。当用氯喹（10^(-6) M）灌注正常大鼠的视网膜时，观察到b波振幅明显且迅速下降。相比之下，氯喹对用PAF拮抗剂BN 50730（30 mg/kg/天，腹腔注射，共5天）预处理的动物分离出的视网膜的b波没有影响。所获得的结果表明：（i）氯喹是一种对视网膜功能有毒的药物；（ii）PAF在氯喹视网膜病变的介导中起关键作用；（iii）PAF拮抗剂可能是治疗这种视网膜损害的有价值的药物。
