Protective effect of a specific PAF antagonist on vincristine-induced experimental retinopathy.

The alkaloid vincristine displays considerable toxicity, particularly for the retina. This type of retinopathy being an inflammatory disease, we measured the effects of a new hetrazepine platelet activating factor antagonist, BN 50730, on a vincristine-induced retinopathy in the rat. Retinal impairments were established by recording several parameters of the electroretinogram obtained from isolated retina. Our results indicate that 1) the increase in PIII duration induced by vincristine is significantly reduced by BN 50730 administration 2) the decrease in the amplitude of the PIII/b wave ratio caused by vincristine is partially inhibited by treatment with BN 50730. These experiments suggest that platelet activating factor is implicated in vincristine retinopathy and demonstrate the therapeutic effect of a specific antagonist of the mediator.

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.

Inhibition of vincristine-induced retinal impairments by a specific PAF antagonist.

The alkaloid vincristine is widely used for its anti-leukemic and anti-tumor activity. However, the drug also displays considerable toxicity, particularly for the retina. Indeed, vincristine has been shown to induce alteration of photoreceptor outer segments in animals and impairment of scotopic vision in man. This type of retinopathy is an inflammatory disease in which PAF may be implicated and for which specific PAF antagonist may have a therapeutic role. Thus, we measured the effects of a new hetrapezine derived PAF antagonist, BN 50730, on a vincristine-induced retinopathy in the rat. Retinal impairments were established by recording several parameters of the electroretinogram (ERG) obtained from isolated retina. Our results indicate that, first, the increase in PIII duration induced by vincristine is significantly reduced by BN 50730 administration and, second, the decrease in the value of the PIII/b wave ratio caused by vincristine is partially inhibited by treatment with BN 50730. These experiments suggest that PAF is implicated in vincristine retinopathy and demonstrate the therapeutic effect of a specific antagonist of the mediator.

[Involvement of PAF (Platelet-Activating Factor) in chloroquine-induced retinopathy]. / Implication du PAF (Platelet-Activating Factor) dans la rétinopathie à la chloroquine.

Chloroquine retinopathy is a severe toxic retinal impairment which may result in loss of vision by alterations of the pigmentary epithelium and photoreceptors. Currently, there is no specific treatment for this retinopathy. In order to test the possible involvement of Platelet-Activating Factor (PAF) in chloroquine-induced retinopathy and the use of PAF antagonists for prevention of this condition, we have examined the effect of these substances on the electroretinogram (ERG) of isolated rat retina. When retinas from normal rats were perfused with chloroquine (10(-6) M), a marked and rapid decrease in ERG b-wave amplitude was observed. In contrast, chloroquine had no effect on the ERG of retina isolated from animals pretreated with the PAF antagonist, BN 50730 (30 mg/kg/day i.p., 5 days). The results obtained indicate that (i) chloroquine is a toxic drug for retinal function, (ii) PAF plays a key role in chloroquine retinopathy and (iii) PAF antagonists may constitute valuable agents for the treatment of this retinal impairment.

[Protective effect of cicletanine in hypertensive retinopathy. Evaluation of retinal function in the isolated retina]. / Effet protecteur du ciclétanine dans la rétinopathie hypertensive. Evaluation de la fonction rétinienne sur rétine isolée.

In order to demonstrate functional impairments related to hypertensive retinopathy, we experimented on the isolated retina of spontaneously hypertensive rats (SHR-SP strain A3N Iffa Credo). We also used this experimental model to assess the protective effect of treatment with cicletanine, a new synthetic furopyridine compound. Treatment consisted of daily oral administration of either 50 or 100 mg/kg of cicletanine for 5 weeks. Retinal function was evaluated by recording the electroretinogram (ERG) obtained in response to light stimulation (300 lux, 1 ms) of the isolated retina maintained in survival by perfusion. The results indicate: (i) that ERG amplitude remains systematically lower in hypertensive rats than in normotensive rats and that in consequence retina survival is shortened; (ii) that in cicletanine-treated hypertensive rats ERG amplitude is significantly higher than in untreated hypertensive rats, the drug augmenting the duration of retina survival. Although cicletanine significantly improved the ERG amplitude obtained in hypertensive rats, this amplitude was still lower than in normotensive rats. These results are consistent with those of previous histological studies performed on the same of hypertensive rats, which demonstrated that impairments of retinal capillaries, photoreceptors and ganglion cells may have deleterious functional consequences for the visual process. Cicletanine is able to reduce these histological impairments, and the present study demonstrate that the drug can also significantly improve the ERG amplitude.