vision/eye
N |
• by P21, mice develop all retinal layers and show normal localization and abundance of outer segment proteins relative to wild-type controls
• at P40-P45, rod photoreceptors produce normal responses to light
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• at 17 months of age, photoreceptor outer segments appear somewhat disorganized, while the inner retina looks normal
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• rods show a defect in photoreceptor disc morphogenesis; newly forming discs are poorly aligned, often contain swollen membrane bulges, and are surrounded by numerous membrane vesicles
• at 2 months of age, extracellular vesicles accumulate in the inter-photoreceptor matrix; these vesicles emanate from the outer segment base where new discs are formed, resulting in a separation of the inner/outer segment juncture
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• at 2 months of age, many rods exhibit an uneven outer segment diameter
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• at 2 months of age, many rods exhibit an uneven outer segment diameter
• newly forming discs do not flatten properly, resulting in the budding of disc-derived extracellular vesicles at the site of disc morphogenesis, which accumulate in the inter-photoreceptor matrix
• however, nascent discs do eventually flatten as they mature and enclose, and the resulting rod outer segments produce normal responses to light
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• at >P21, mice exhibit a slow progressive degeneration of rod photoreceptors, with ~36% of photoreceptors lost by 17 months of age
• however, no decrease in cone cell numbers is observed up to 17 months of age
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• immunogold analysis suggests that RPE, normally involved in phagocytosis of shed outer segment material, lacks the capacity to clear the disc-derived vesicles from the inter-photoreceptor matrix
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• outer nuclear layer (ONL) thickness is normal at P21 but significantly decreased at 17 months of age
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nervous system
• activated microglia show a unique pattern of migration to the site of extracellular vesicle accumulation; the vast majority of phagocytes observed in the photoreceptor layer are resident microglia with only 4% being monocyte-derived macrophages
• whereas many microglial cells are found in the ONL at P21, most microglia settle at the inner/outer segment junction by 4 months of age where they actively phagocytize vesicles
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• at 17 months of age, photoreceptor outer segments appear somewhat disorganized, while the inner retina looks normal
|
• rods show a defect in photoreceptor disc morphogenesis; newly forming discs are poorly aligned, often contain swollen membrane bulges, and are surrounded by numerous membrane vesicles
• at 2 months of age, extracellular vesicles accumulate in the inter-photoreceptor matrix; these vesicles emanate from the outer segment base where new discs are formed, resulting in a separation of the inner/outer segment juncture
|
• at 2 months of age, many rods exhibit an uneven outer segment diameter
|
• at 2 months of age, many rods exhibit an uneven outer segment diameter
• newly forming discs do not flatten properly, resulting in the budding of disc-derived extracellular vesicles at the site of disc morphogenesis, which accumulate in the inter-photoreceptor matrix
• however, nascent discs do eventually flatten as they mature and enclose, and the resulting rod outer segments produce normal responses to light
|
• at >P21, mice exhibit a slow progressive degeneration of rod photoreceptors, with ~36% of photoreceptors lost by 17 months of age
• however, no decrease in cone cell numbers is observed up to 17 months of age
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immune system
• activated microglia show a unique pattern of migration to the site of extracellular vesicle accumulation; the vast majority of phagocytes observed in the photoreceptor layer are resident microglia with only 4% being monocyte-derived macrophages
• whereas many microglial cells are found in the ONL at P21, most microglia settle at the inner/outer segment junction by 4 months of age where they actively phagocytize vesicles
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pigmentation
• immunogold analysis suggests that RPE, normally involved in phagocytosis of shed outer segment material, lacks the capacity to clear the disc-derived vesicles from the inter-photoreceptor matrix
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hematopoietic system
• activated microglia show a unique pattern of migration to the site of extracellular vesicle accumulation; the vast majority of phagocytes observed in the photoreceptor layer are resident microglia with only 4% being monocyte-derived macrophages
• whereas many microglial cells are found in the ONL at P21, most microglia settle at the inner/outer segment junction by 4 months of age where they actively phagocytize vesicles
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