Propagation and Selectivity of Axonal Loss in Leber Hereditary Optic Neuropathy
| العنوان: | Propagation and Selectivity of Axonal Loss in Leber Hereditary Optic Neuropathy |
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| المؤلفون: | Razek Georges Coussa, Pooya Merat, Leonard A. Levin |
| المصدر: | Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, LEBER HEREDITARY OPTIC NEUROPATHY, genetic structures, Models, Neurological, Axonal loss, lcsh:Medicine, Optic Atrophy, Hereditary, Leber, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Superoxides, medicine, Humans, Computer Simulation, Axon, Author Correction, lcsh:Science, Multidisciplinary, Extramural, lcsh:R, Reproducibility of Results, Hereditary eye disease, Optic Nerve, Axons, eye diseases, 030104 developmental biology, medicine.anatomical_structure, nervous system, Optic nerve diseases, Central vision, Optic nerve, lcsh:Q, Axonal degeneration, Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | Leber hereditary optic neuropathy (LHON) is a syndrome of subacute loss of central vision associated with mutations in mitochondrial DNA coding for components of complex I. LHON preferentially involves small axons in the temporal optic nerve, but the reason is unclear. We performed a Monte Carlo simulation of the spread of injury in LHON axons to better understand the predilection for small axons. Optic nerve slices were modeled as grids containing axons with sizes from reported regional distributions. The propagation of injury from a localized concentration of superoxide was simulated as the spread via passive diffusion from one axon to adjacent axons, with basal production and scavenging rate proportional to axonal area and volume, respectively. Axonal degeneration occurred when intra-axonal concentrations reached a toxic threshold. Simulations demonstrated that almost all small and medium axons degenerated by the time steady-state was reached, but about 50% of large axons were preserved. The location of initial injury affected time to steady state, with nasal injuries reaching steady state faster than temporal injuries. The pattern of axonal degeneration in the simulations mirrored both visual fields and optic nerve histology from patients with LHON. These results provide insight into the nature of axonal loss in LHON. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::af530522b3f7c34d4c3702659a150544Test http://link.springer.com/article/10.1038/s41598-019-43180-zTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....af530522b3f7c34d4c3702659a150544 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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