Neurodegeneration
Glaucoma pathology follows a distal-to-proximal progression similar to other "dying back" neuropathies. Key events defining RGC degeneration in glaucoma span four critical regions: retina, optic nerve head, optic nerve and tract, and the central projection to the brain. Glaucoma-relevant stress originates in the optic nerve head (2) and triggers a program of degeneration that includes failure of axonal transport to the central projections (4), degeneration of RGC axons in the optic nerve and tract (3), and eventual somatic drop-out in the retina (1) . For more information, please see Calkins and Horner 2012, Calkins 2012, Crish 2010 on Publication page.
Optic nerve head
A major site of injury in glaucoma is the optic nerve head (ONH). Shown to the left are ONH images from saline and microbead injected eyes. Three hallmarks of the disease can be seen in these images: (1) a cupping of the ONH in the microbead eye (dotted line) compared to the saline injected eye; (2) GFAP (red) upregulation by reactive astrocytes (asterisks); (3) and the activation of microglia (blue) as shown by loss of ramification (arrowheads).Central Projections
An early sign of RGC degeneration is deficits in anterograde transport to targets in the brain. For more information on axonal transport analysis, please see the Outcome Measures section in our Toolbox. Axonal transport to the superior colliculus (SC) decreases with age in DBA mice (top panels) and in aged rats following microbead injection to elevate IOP (bottom panels). For retinotopic SC maps the optic disk gap (circle), rostral (R), caudal (C), and medial (M) are indicated; IOP for DBA mice in mmHg is indicated. CTB signal density varies from 100% (red) to 50% (green) to 0% (blue). For more information see Crish 2010 on Publication page.
Optic nerve and tract
Cross-sections through proximal and distal segments of the optic nerve of a 13 month DBA shows degenerating profiles (top left; arrowheads). Axon degeneration begins distally, as more degenerating profiles/section are seen in the distal segment (top right). Microbead injection to elevate IOP also results in axon degeneration (bottom left) and a reduction in axon density and total axon number (bottom right). For more information see Sappington 2010 and Crish 2010 on Publication page.
Pruning of RGC dendritic trees occurs during glaucomatous progression. RGC dendritic trees from 3 month DBA retinas look similar to those from C57 retinas, with complex branching patterns (top), while dendritic trees of RGCs from 10 month DBA retinas appeared less complex, with fewer overall branches. Analysis of dendritic morphology (for more information see our Toolbox) shows a reduction in dendritic length and dendritic field area in 10 month DBA retinas compared to 3 month DBA or C57 retinas.