Abstract
Rod and cone photoreceptors initiate the visual process by capturing photons and transducing the information into chemical and electrical signals. These functionally specialized neurons have high metabolic activity and oxygen consumption, making them vulnerable to genetic insults and changes in microenvironment. Inherited retinal degenerative diseases are clinically and genetically heterogeneous, with more than 200 genes identified so far. In a majority of retinal degenerations, the genetic defects affect diverse functions in photoreceptors, such as phototransduction, gene regulation, splicing, or intracellular transport. To develop efficient therapies, it is critical to elucidate how genetic defects affect cellular functions and activate death pathways. Caspase-dependent and -independent apoptosis appear to be the major route for photoreceptor cell death in retinal diseases, although the importance of necrosis and autophagy has been demonstrated. Distinct molecules associated with oxidative or endoplasmic reticulum stress can activate these interconnected cell death pathways. Notably, in most inherited diseases, the first signs of photoreceptor dysfunction or loss are observed years after birth and late in life, indicating adaptive mechanisms that protect the cells and suggesting their breakdown may lead to cell death. Mitochondria are predicted to play a critical role in integrating cellular homeostasis to stress and initiation of death pathways. Investigations of adaptive behavior and pre-death molecules that modulate the response to genetic factors should provide attractive targets for the development of better therapeutic approaches.
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Roger, J.E., Swaroop, A. (2014). Photoreceptor Degeneration: Molecular Mechanisms of Photoreceptor Degeneration. In: Furukawa, T., Hurley, J., Kawamura, S. (eds) Vertebrate Photoreceptors. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54880-5_11
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