A Re-Appraisal of Pathogenic Mechanisms Bridging Wet and Dry Age-Related Macular Degeneration Leads to Reconsider a Role for Phytochemicals
| Autor: | Carla L. Busceti, Maico Polzella, Francesco Fornai, Roberto Pinelli, Miorica Bertelli, Elena Scaffidi, Fiona Limanaqi, Francesca Biagioni |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cell type
autophagy Cell Phytochemicals retinal pigment epithelium Review Biology Drusen resveratrol Catalysis Retina lcsh:Chemistry Inorganic Chemistry immunoproteasome Macular Degeneration retinopathy medicine oxidative stress Humans Photoreceptor Cells Physical and Theoretical Chemistry lcsh:QH301-705.5 Molecular Biology Spectroscopy lutein Retinal pigment epithelium Choroid Organic Chemistry Autophagy General Medicine Macular degeneration medicine.disease eye diseases Computer Science Applications Cell biology medicine.anatomical_structure proteasome lcsh:Biology (General) lcsh:QD1-999 Proteasome inflammation sense organs Immunoproteasome Inflammation Lutein Oxidative stress Resveratrol Retinopathy Oxidation-Reduction Intracellular |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 21, Iss 5563, p 5563 (2020) |
| ISSN: | 1422-0067 |
| Popis: | Which pathogenic mechanisms underlie age-related macular degeneration (AMD)? Are they different for dry and wet variants, or do they stem from common metabolic alterations? Where shall we look for altered metabolism? Is it the inner choroid, or is it rather the choroid–retinal border? Again, since cell-clearing pathways are crucial to degrade altered proteins, which metabolic system is likely to be the most implicated, and in which cell type? Here we describe the unique clearing activity of the retinal pigment epithelium (RPE) and the relevant role of its autophagy machinery in removing altered debris, thus centering the RPE in the pathogenesis of AMD. The cell-clearing systems within the RPE may act as a kernel to regulate the redox homeostasis and the traffic of multiple proteins and organelles toward either the choroid border or the outer segments of photoreceptors. This is expected to cope with the polarity of various domains within RPE cells, with each one owning a specific metabolic activity. A defective clearance machinery may trigger unconventional solutions to avoid intracellular substrates’ accumulation through unconventional secretions. These components may be deposited between the RPE and Bruch’s membrane, thus generating the drusen, which remains the classic hallmark of AMD. These deposits may rather represent a witness of an abnormal RPE metabolism than a real pathogenic component. The empowerment of cell clearance, antioxidant, anti-inflammatory, and anti-angiogenic activity of the RPE by specific phytochemicals is here discussed. |
| Databáze: | OpenAIRE |
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