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Editors Selection IGR 17-4
Basic Research: Astrocytes and maintenance of RGC health
Comment by Adriana DiPolo on:
27891 Myelination transition zone astrocytes are constitutively phagocytic and have synuclein dependent reactivity in glaucoma, Nguyen JV; Soto I; Kim K-Y et al., Proceedings of the National Academy of Sciences of the United States of America, 2011; 108: 1176-1181
The optic nerve head (ONH) and the lamina cribrosa have long been considered a crucial site in the onset of glaucomatous damage. Astrocytes in the ONH undergo dramatic changes in glaucoma including reactive gliosis, hypertrophy, and increased migration. However, the precise contribution of ONH astrocytes to neurodegeneration in glaucoma remains a mystery. What do astrocytes in the ONH normally do, and how are these functions perturbed in glaucoma?
Nguyen et al. (359) characterized a discrete population of ONH astrocytes, those at the myelination transition zone (MTZ). They showed that MTZ astrocytes express high levels of Mac-2, a molecule implicated in myelin phagocytosis by cells with phagocytic properties such as microglia and Schwann cells.
The intriguing observation that astrocytes in the ONH normally phagocytose axonal processes suggests that this might be an important process for the overall maintenance of retinal ganglion cell health
Mac-2 expression in ONH astrocytes substantially increased in DBA/2J mice, a spontaneous model of glaucoma. Using automated serial block-face scanning EM, the authors report that ONH astrocytes, including those at the MTZ, constitutively phagocytose retinal ganglion cell axons. Axonal protrusions and evulsions, axonal material found inside Mac-2 expressing astrocytes, contained a protease-resistant form of γ-synuclein. MTZ astrocytes in knockout mice lacking γ-synuclein failed to upregulate Mac-2 after elevation of intraocular pressure, suggesting that increased astrocytic Mac-2 expression is dependent on γ-synuclein. What are the implications of these findings? Firstly, the intriguing observation that astrocytes in the ONH normally phagocytose axonal processes suggests that this might be an important process for the overall maintenance of retinal ganglion cell health.
Secondly, the accumulation of protease resistant γ-synuclein in animal models glaucoma suggests that aggregated γ-synuclein might contribute to retinal ganglion cell loss in this disease. Of interest, a pathological link between protease resistant γ-synuclein and Parkinson's disease and other synucleinopathies has been established.
A pathological link between protease resistant -synuclein and Parkinson's disease and other synucleinopathies has been established
Thirdly, failure of ONH astrocytes to clear axonal debris or to prune axons might lead to accumulation of toxic proteins, such as γ-synuclein, which could contribute to retinal ganglion cell loss in glaucoma. Whether this mechanism plays a role in glaucoma still remains to be demonstrated, however, this study uncovers a novel role for ONH astrocytes that could lead to key insights into their contribution to neurodegeneration.
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