PHAGOCYTIC ASTROCYTES AND THE FORMATION OF LIPID DROPLETS IN THE MYELINATION TRANSITION ZONE OF THE OPTIC NERVE HEAD IN THE DBA/2J MOUSE GLAUCOMA MODEL
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Date
2014-08-05
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Johns Hopkins University
Abstract
Glaucoma is a progressive disease that results in the degeneration of retinal ganglion cells and their axons, which make up the optic nerve. From the comparative analysis of degeneration patterns in the retina and of the axons directly exiting the retina, it has been proposed that damage to the axons in the optic nerve head occurs before the loss of retinal ganglion cells. Therefore, the focus of this dissertation was to identify biology in the optic nerve head that might contribute to the development of glaucoma.
The phagocytic activity of astrocytes was discovered by studying the effects of disease and injury on the cells in the optic nerve using genetic and acute mouse models. These astrocytes were initially identified by the expression of Lgals3, a phagocytosis-related gene more commonly found in phagocytes. Astrocytes had specific Lgals3 expression in the myelination transition zone that increased in mouse models of glaucoma. Further analysis of myelination transition zone astrocytes using electron microscopy revealed the presence of axonal debris, myelin remnants, and lipid droplets inside the astrocyte cytoplasm. Primary astrocyte cultures demonstrated that continuous and repeated phagocytosis of myelin induced lipid droplet formation.
These studies describe a dynamic role of astrocytes in optic nerve biology. Optic nerve astrocytes actively phagocytose myelin and, in disease, do so to the point that the myelin accumulates within the cell and lipid droplets form. Further investigations of myelin stability and astrocyte phagocytosis may lead to new clues in the progression of axon damage, while understanding lipid droplet biology in the optic nerve might lead to the identification of biomarkers in glaucoma.
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glaucoma, optic nerve, astrocytes, phagocytosis, lipid droplets