Quantitative modeling of rod outer segment phagocytosis and recycling
Abstract There is continual turnover of macromolecules as part of maintenance. This allows removal of damaged macromolecules and their replacement. A prime example is the turnover of the rod photoreceptor outer segment. Every day, 10% of rod photoreceptor outer segments is phagocytosed by the neighb...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-06356-4 |
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| author | Christina Kiel Alexander J. E. Foss |
| author_facet | Christina Kiel Alexander J. E. Foss |
| author_sort | Christina Kiel |
| collection | DOAJ |
| description | Abstract There is continual turnover of macromolecules as part of maintenance. This allows removal of damaged macromolecules and their replacement. A prime example is the turnover of the rod photoreceptor outer segment. Every day, 10% of rod photoreceptor outer segments is phagocytosed by the neighboring retinal pigment epithelium cells where they undergo phagolysosomal degradation. For example, the proteins are broken down to their component amino acids. These components need to be efficiently recycled back to the rod photoreceptor, while the damaged components can be eliminated. These damaged molecules need to be replaced either by synthesis or from the circulation. Here, we calculate the demand fluxes for the different turnover processes relevant for outer segment phagocytosis. We show that the breakdown of proteins poses a potential osmotic problem. We develop computational models of rhodopsin digestion and recycling, which show that the duration of phagocytosis, digestion, and recycling of molecular components occur on a just in time basis. These findings imply that even modest impairments in lysosomal function, changes in protein abundances of key degradative enzymes or metabolite transporters could disrupt this fine-tuned process with potential consequences for photoreceptor survival. |
| format | Article |
| id | doaj-art-91ce859c2df1494c89024dc28a73304f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-91ce859c2df1494c89024dc28a73304f2025-08-20T03:45:30ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-06356-4Quantitative modeling of rod outer segment phagocytosis and recyclingChristina Kiel0Alexander J. E. Foss1Department of Molecular Medicine, University of PaviaDepartment of Ophthalmology, Nottingham University Hospitals NHS TrustAbstract There is continual turnover of macromolecules as part of maintenance. This allows removal of damaged macromolecules and their replacement. A prime example is the turnover of the rod photoreceptor outer segment. Every day, 10% of rod photoreceptor outer segments is phagocytosed by the neighboring retinal pigment epithelium cells where they undergo phagolysosomal degradation. For example, the proteins are broken down to their component amino acids. These components need to be efficiently recycled back to the rod photoreceptor, while the damaged components can be eliminated. These damaged molecules need to be replaced either by synthesis or from the circulation. Here, we calculate the demand fluxes for the different turnover processes relevant for outer segment phagocytosis. We show that the breakdown of proteins poses a potential osmotic problem. We develop computational models of rhodopsin digestion and recycling, which show that the duration of phagocytosis, digestion, and recycling of molecular components occur on a just in time basis. These findings imply that even modest impairments in lysosomal function, changes in protein abundances of key degradative enzymes or metabolite transporters could disrupt this fine-tuned process with potential consequences for photoreceptor survival.https://doi.org/10.1038/s41598-025-06356-4ATPEnergy budgetOuter retinaPhagocytosisPhotoreceptorRhodopsin |
| spellingShingle | Christina Kiel Alexander J. E. Foss Quantitative modeling of rod outer segment phagocytosis and recycling Scientific Reports ATP Energy budget Outer retina Phagocytosis Photoreceptor Rhodopsin |
| title | Quantitative modeling of rod outer segment phagocytosis and recycling |
| title_full | Quantitative modeling of rod outer segment phagocytosis and recycling |
| title_fullStr | Quantitative modeling of rod outer segment phagocytosis and recycling |
| title_full_unstemmed | Quantitative modeling of rod outer segment phagocytosis and recycling |
| title_short | Quantitative modeling of rod outer segment phagocytosis and recycling |
| title_sort | quantitative modeling of rod outer segment phagocytosis and recycling |
| topic | ATP Energy budget Outer retina Phagocytosis Photoreceptor Rhodopsin |
| url | https://doi.org/10.1038/s41598-025-06356-4 |
| work_keys_str_mv | AT christinakiel quantitativemodelingofrodoutersegmentphagocytosisandrecycling AT alexanderjefoss quantitativemodelingofrodoutersegmentphagocytosisandrecycling |