Chapter 10 - Retinal ganglion cell dendrite pathology and synapse loss: Implications for glaucoma

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Abstract

Dendrites are exquisitely specialized cellular compartments that critically influence how neurons collect and process information. Retinal ganglion cell (RGC) dendrites receive synaptic inputs from bipolar and amacrine cells, thus allowing cell-to-cell communication and flow of visual information. In glaucoma, damage to RGC axons results in progressive neurodegeneration and vision loss. Recent data indicate that axonal injury triggers rapid structural alterations in RGC dendritic arbors, prior to manifest axonal loss, which lead to synaptic rearrangements and functional deficits. Here, we provide an update on recent work addressing the role of RGC dendritic degeneration in models of acute and chronic optic nerve damage as well as novel mechanisms that regulate RGC dendrite stability. A better understanding of how defects in RGC dendrites contribute to neurodegeneration in glaucoma might provide new insights into disease onset and progression, while informing the development of novel therapies to prevent vision loss.

Section snippets

Does Dendritic Pathology Contribute to Vision Loss in Glaucoma?

During normal visual processing, retinal ganglion cell (RGC) dendrites receive synaptic inputs from bipolar and amacrine cells in the inner plexiform layer. This information is integrated, processed, and sent via RGC axons in the optic nerve to visual centers in the brain (Masland, 2012). The structural integrity of dendrites is essential for vision. Dendrites allow communication between RGCs and other retinal neurons via synapses. Furthermore, dendrites integrate and propagate input signals to

Morphological Diversity of RGC Dendrites: An Embarrassment of Riches

Newly born RGCs initiate an axon that grows along the nerve fiber layer lining the innermost surface of the retina, then exits the eye via the ONH, and extends into the optic nerve proper to reach targets in the brain (Bao, 2008, Haupt and Huber, 2008). As RGC axons enter the brain, dendrites begin to grow from the cell soma extending through the inner plexiform layer to form synapses with bipolar and amacrine cell processes (Choi et al., 2010, Holt, 1989). Primary dendrites then branch to

Axonal Injury Triggers Pathological Changes in RGC Dendrites

Changes in RGC dendrites have been historically perceived as anecdotal or intriguing at most. Indeed, very few studies on RGC dendritic alterations in models of optic nerve damage were published before 2010. Among these were the pioneering work by Weber and colleagues describing early structural abnormalities in RGC dendrites in a nonhuman primate model of chronic IOP elevation (Weber et al., 1998). In this study, parasol cells in glaucomatous eyes showed a significant reduction in dendritic

Mechanisms That Regulate Dendrite and Synapse Stability

Despite the fact that dendritic and synaptic defects are likely to have devastating consequences on neuronal function and survival, the mechanisms that regulate RGC dendrite degeneration in glaucoma are vastly unknown. A better understanding of the molecular pathways that regulate dendritic stability or loss is critical for the development of targeted therapies to maintain or enhance RGC connectivity and function. The next sections describe new findings on molecular pathways that regulate RGC

Conclusions and Future Directions

In recent years, there has been a tangible increase in the number of studies investigating RGC dendritic abnormalities triggered by axonal injury. Emerging data indicate that damage to RGC axons, by ocular hypertension or acute insults, triggers rapid, and marked dendritic modifications. Most studies agree that the primary changes involve dendritic retraction, characterized by a reduction in dendritic field area, process length, and arbor complexity. The consensus is that these dendritic

Acknowledgments

This work was supported by grants to A.D.P. from the Canadian Institutes of Health Research (CIHR). We thank Dr. Timothy E. Kennedy for comments on the manuscript, and Mr. James Correia for assistance with the figure.

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