THE MELATONIN ANTAGONIST LUZINDOLE PROTECTS RETINAL PHOTORECEPTORS FROM LIGHT DAMAGE IN THE RAT

PURPOSE. Systemic administration of melatonin can increase retinal lig ht damage in the rat. The role of retinal melatonin receptors in modul ating Light-damage susceptibility was investigated by intravitreally i njecting the melatonin receptor antagonist luzindole into rats. METHOD S. 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 mu l 1 mM luzindole in one eye and 1 mu l vehicle in t he 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 we re exposed to constant light of 2500 lux for 48 hours. Animals were re turned to dim cyclic light for 7 days, and dark-adapted electroretinog rams (ERGs) were then recorded from the two eyes simultaneously. The e yes were processed for retinal morphology. Photoreceptor nuclei were c ounted in the outer nuclear layer (ONL), and the thickness of the ONL and that of the rod outer-segment plus inner-segment layer were measur ed at several points along sections through the vertical meridian. Two age-matched control rats were maintained in dim cyclic light but rece ived no injections. RESULTS. Luzindole-treated eyes had ERG b-wave thr esholds of 2.7 +/- 0.5 (mean +/- SEM) log candela (cd)/m(2) lower than the fellow eyes injected with vehicle (P < 0.001), and the maximum b- wave amplitude was 1.0 +/- 0.2 log mu V greater in luzindole-treated e yes (P < 0.001). Thresholds of the scotopic threshold response were 0. 5 +/- 0.1 log cd/m(2) lower than those in vehicle-injected eyes (P < 0 .05). Luzindole-treated eyes on average had twice as many photorecepto r cells remaining (P < 0.005). Ln some areas, several rows of photorec eptor nuclei and outer segments remained in the luzindole-treated eye, whereas the fellow control eye showed cells only occasionally and no outer segments. CONCLUSIONS. Eyes pretreated with the melatonin recept or competitive antagonist luzindole before the dark phase preceding co nstant light exposure were substantially protected from light damage t o the retinal photoreceptors. These results implicate the intraocular melatonin-dopamine system in the regulation of light-damage susceptibi lity.