Accumulation of lipid inclusions in astrocytes of aging human optic nerve
ABSTRACT We examined age-related changes in the human optic nerve (ON) from 10 postmortem donor eye samples (age: 21- to 94-year-old). In aged ON, many axons showed paucity of cytoskeleton, and possessed disorganized myelin that remained in the extracellular space. Lipid inclusions were detected in glia, as stained by oil red O, and these accumulated with aging. To identify and confirm which glial cell type possessed lipid inclusions, we performed immunohistochemistry (IHC) and transmission electron microscopy (TEM). Comparisons were made from TEM features and size of the glia immunolabeled with glial fibrillary acidic protein and glutamine synthetase (markers for astrocytes) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (a marker for oligodendrocytes). It was found that lipid inclusions were restricted to the astrocytes having larger perikarya than the oligodendrocytes (IHC) and possessing filaments in cytoplasm (TEM). These astrocytes also possessed myelin debris and it is thus likely that those inclusions originated from degenerated myelin of the ON axons. These data indicate that astrocytes play a role in phagocytosis and clearance of disorganized myelin in aging human ON.
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ABSTRACT: The relative rate of rod and cone degeneration is a fundamental characteristic of any disorder affecting photoreceptors, including ageing and age-related maculopathy (ARM). The macula consists of a small cone-dominated fovea surrounded by a rod-dominated parafovea. In donor eyes with grossly normal maculas, the number of foveal cones is stable and the number of parafoveal rods decreases by 30% over adulthood. These trends continue in early ARM. In exudative ARM, the photoreceptors that survive over disciform scars are largely cones, and rods decline precipitously in relation to thick subretinal pigment epithelium deposits. The preferential vulnerability of rods over cones has been confirmed by recent functional studies showing that the loss of scotopic sensitivity is greater than the loss of photopic sensitivity throughout adulthood and in patients with early ARM. A hypothesis that these effecfs are due to to retinoid deficiency at the level of the photoreceptors is proposed. The topography of rod loss in ageing and ARM is consistent with the location of early ARM lesions described in population-based studies and is not consistent with the location of fundus autofluorescence due to lipofuscin.Eye 07/2001; 15(Pt 3):376-83. DOI:10.1038/eye.2001.140 · 1.90 Impact Factor
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ABSTRACT: The optic nerve is a circumscribed white matter tract consisting of myelinated nerve fibers and neuroglial cells. Previous work has shown that during normal aging in the rhesus monkey, many optic nerves lose some of their nerve fibers, and in all old optic nerves there are both myelin abnormalities and degenerating nerve fibers. The present study assesses how the neuroglial cell population of the optic nerve is affected by age. To address this question, optic nerves from young (4-10 years) and old (27-33 years) rhesus monkeys were examined by using both light and electron microscopy. It was found that with age the astrocytes, oligodendrocytes, and microglia all develop characteristic cytoplasmic inclusions. The astrocytes hypertrophy and fill space vacated by degenerated nerve fibers, and they often develop abundant glial filaments in their processes. Oligodendrocytes and microglial cells both become more numerous with age, and microglial cells often become engorged with phagocytosed debris. Some of the debris can be recognized as degenerating myelin, and in general, the greater the loss of nerve fibers, the more active the microglial cells become.The Journal of Comparative Neurology 03/2002; 445(1):13-28. DOI:10.1002/cne.10162 · 3.51 Impact Factor
- Physiological Reviews 02/1968; 48(1):197-251. · 29.04 Impact Factor