Melatonin rescues visual and behavioral deficits in rd10 mouse model of retinal degeneration

Abstract

Introduction: Retinal degeneration 10 (rd10) is a mouse model of retinitis pigmentosa with rapid retinal photoreceptors degeneration. Although, recent study has demonstrated the delay of photoreceptors degeneration by melatonin treatment in rd10 mice, the mechanisms by which melatonin induced neuroprotection remained largely obscure. Materials and Methods: Four weeks-old male rd10 mice received 28 days of intraperitoneal melatonin (10 mg/kg) treatment, and animals were behaviourally tested for changes of anxiety, social and visual memory performances. For mechanisms, electrophysiological and morphological/biochemical studies were conducted to further evaluate the neuroprotective effects of melatonin in this rd10 model. Results and Discussion: Our results demonstrated that melatonin treatment rescued the rd10 behavioural deficits of anxiety, social and visual memory function as measured by the novelty-suppressed feeding test, social memory and visual memory tests. To validate these findings, experiments with temozolomide treatment revealed that the behavioural improvement by melatonin was mediated through both the neuroplasticity-dependent and -independent mechanisms. Interestingly, we also observed that melatonin restored the visual-evoked potentials recorded from neurons in the primary visual cortex; and improved the a- and b-waves in electroretinography, indicating that melatonin treatment retained the functional interaction and integrity between the retina and visual-cortical connection while protecting the retinal photoreceptors. Finally, these results were further supported by morphological/biochemical studies related to neuroplasticity-related mechanisms in the retina, visual cortex and hippocampus. Conclusion: Our findings suggest that melatonin could be a potential therapeutic drug in rescuing visual and behavioural deficits through neuroplasticity-dependent and -independent mechanisms in retinal degeneration.