All-trans-retinal (atRAL) is a one of the major vitamin A metabolites in the retina. In physiological conditions, all-trans-RAL is regenerated to the visual chromophore, 11-cis-retinal. Necrosis was demonstrated not to be the main pathway in atRAL mediated cell death. Bcl-2-interacting mediator and Bcl-2 expression levels were not altered by atRAL in vitro. atRAL-induced oxidative stress results in DNA damage leading to the activation of Bax by phosphorylated p53[1]. Phosphorylation of JNK (c-Jun N-terminal kinase) in atRAL-loaded photoreceptor cells induced the appearance of γH2AX, a sensitive marker for DNA damage, and was also associated with apoptosis onset[2].Photoactivated 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[3].
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