Abstract
Purpose: :
Light is essential for visual perception to isomerize cis-retinyl imine chromophore to its trans isomer of cone opsin and rhodopsin. However, light can also accelerate photoreceptor cell death by apoptosis. Even though light has been proposed as a risk factor for many eye diseases, including age-related macular degeneration and retinitis pigmentosa, the signaling mechanisms that lead to degeneration are not understood at the molecular level. Retinal melatonin is down-regulated by light and is barely detectable during the day. It is possible that the absence of melatonin in the retina during prolonged light exposure causes or contributes to light-induced retinal degeneration. We sought to investigate the impact of melatonin in light-exposed retina using proteomic approaches.
Methods: :
We exposed mice to light (250-300 lux) for 12 hours followed by 12 hours darkness or the same intensity of continuous light. In half of the animals that have been exposed to continuous light, melatonin was injected during each subjective night. Proteomic analysis of the retinas from these three groups of animals showed that five proteins prominently up-regulated by constant light were down-regulated by melatonin treatment.
Results: :
These five proteins were identified as vimentin, serine/threonine-protein phosphatase 2A, rab GDP dissociation inhibitor alpha, guanine nucleotide-binding protein G (o) subunit alpha and retinaldehyde-binding protein. These five proteins are known to be involved in several cellular processes that may contribute to light-induced retinal degeneration. Identification of melatonin target proteins in our study provides basis for future studies on melatonin’s potential in preventing or treating light induced retinal degeneration.
Conclusions: :
Our study unambiguously demonstrates that in vivo supplementation of melatonin to mice with constant light-exposed retinas partially reverses light-induced protein changes. Since constant light eventually results in retinal dysfunction and degeneration and since human beings are more and more often exposed to light at night, this study provides good reason for us to better understand constant light-induced retinal pathologies as well as whether and how melatonin at night might alleviate them.
Keywords: proteomics • retina • melatonin