Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice

• Published in: The Journal of cell biology Vol. 171; no. 2; pp. 313 - 325
• Main Authors: Jakobs, Tatjana C, Libby, Richard T, Ben, Yixin, John, Simon W.M, Masland, Richard H
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 24-10-2005; The Rockefeller University Press
• Subjects: Amacrine cells; Amacrine Cells - pathology; Animals; Axons; Cell Count; Cell nucleus; Cell Shape; Cells; Dendrites; Disease Models, Animal; Disease Progression; Ganglia; Glaucoma; Glaucoma - genetics; Glaucoma - pathology; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Nerves; Neurons; Optic nerve; Retina; Retinal Bipolar Cells - pathology; Retinal Degeneration - pathology; Retinal Ganglion Cells - pathology; Rodents
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200506099

Using a variety of double and triple labeling techniques, we have reevaluated the death of retinal neurons in a mouse model of hereditary glaucoma. Cell-specific markers and total neuron counts revealed no cell loss in any retinal neurons other than the ganglion cells. Within the limits of our ability to define cell types, no group of ganglion cells was especially vulnerable or resistant to degeneration. Retrograde labeling and neurofilament staining showed that axonal atrophy, dendritic remodeling, and somal shrinkage (at least of the largest cell types) precedes ganglion cell death in this glaucoma model. Regions of cell death or survival radiated from the optic nerve head in fan-shaped sectors. Collectively, the data suggest axon damage at the optic nerve head as an early lesion, and damage to axon bundles would cause this pattern of degeneration. However, the architecture of the mouse eye seems to preclude a commonly postulated source of mechanical damage within the nerve head.