Accumulation of all-trans-retinal (all-trans-RAL), reactive vitamin A aldehyde, is one of the key factors in initiating retinal photodamage. This photodamage is characterized by progressive retinal cell death evoked by light exposure in both an acute and chronic fashion. Photo-activated rhodopsin releases all-trans-RAL which is subsequently transported by ATP–binding cassette transporter 4 and reduced to all-trans-retinol by all-trans-retinol dehydrogenases located in photoreceptor cells. Any interruptions in the clearing of all-trans-RAL in the photoreceptors can cause an accumulation of this reactive aldehyde and its toxic condensation products. This accumulation may result in the manifestation of retinal dystrophy including human retinal degenerative diseases such as Stargardt’s disease and age-related macular degeneration. Here, we discuss the mechanisms of all-trans-RAL clearance in photoreceptor cells by sequential enzymatic reactions, the visual (retinoid) cycle, and potential molecular pathways of retinal photodamage. We also review recent imaging technologies to monitor retinal health status as well as novel therapeutic strategies preventing all-trans-RAL-associated retinal photodamage.
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