The melatonin antagonist luzindole protects retinal photoreceptors from light damage in the rat

Systemic administration of melatonin can increase retinal light damage in the rat. The role of retinal melatonin receptors in modulating light-damage susceptibility was investigated by intravitreally injecting the melatonin receptor antagonist luzindole into rats.

Nine Sprague-Dawley albino rats 8 to 9 weeks of age were kept in 50 lux cyclic light for at least 7 days before receiving an intravitreal injection of 1 microl 1 mM luzindole in one eye and 1 microl vehicle in the other eye. The injection was given just before the beginning of the normal 12-hour dark phase. At the end of this dark period, animals were exposed to constant light of 2500 lux for 48 hours. Animals were returned to dim cyclic light for 7 days, and dark-adapted electroretinograms (ERGs) were then recorded from the two eyes simultaneously. The eyes were processed for retinal morphology. Photoreceptor nuclei were counted in the outer nuclear layer (ONL), and the thickness of the ONL and that of the rod outer-segment plus inner-segment layer were measured at several points along sections through the vertical meridian. Two age-matched control rats were maintained in dim cyclic light but received no injections.

Luzindole-treated eyes had ERG b-wave thresholds of 2.7 +/- 0.5 (mean +/- SEM) log candela (cd)/m2 lower than the fellow eyes injected with vehicle (P < 0.001), and the maximum b-wave amplitude was 1.0 +/- 0.2 log microV greater in luzindole-treated eyes (P < 0.001). Thresholds of the scotopic threshold response were 0.5 +/- 0.1 log cd/m2 lower than those in vehicle-injected eyes (P < 0.05). Luzindole-treated eyes on average had twice as many photoreceptor cells remaining (P < 0.005). In some areas, several rows of photoreceptor nuclei and outer segments remained in the luzindole-treated eye, whereas the fellow control eye showed cells only occasionally and no outer segments.

Eyes pretreated with the melatonin receptor competitive antagonist luzindole before the dark phase preceding constant light exposure were substantially protected from light damage to the retinal photoreceptors. These results implicate the intraocular melatonin-dopamine system in the regulation of light-damage susceptibility.