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The Role of NMDA Receptor Activity in Retinal Ganglion Cell Dendrite Development

Scientific poster example

 

This abstract was presented today at the 2014 Association for Research in Vision and Opthalmology (ARVO) meetings in Orlando, Florida by Eerik M. Elias, Ping Wang and Ning Tian.

Full size poster available here.

Purpose: To elucidate mechanisms underlying the dendrite developmental plasticity of retinal ganglion cells, we examined the role of glutamate receptors on retinal ganglion cell dendrite elongation and filopodia elimination.

Methods: We used the JamB genetically labeled subtype of RGCs as our working model. JamB-CreER:YFP ganglion cell dendritic arbors were imaged in whole mount retina using confocal microscopy. Dendrite length, area, branching, and filopodia number were traced and measured using Neurolucida. Visual inputs were blocked by dark-rearing pups after P5. Glutamatergic activity was blocked using daily intraocular injections of AP5 and CNQX from P9 to P13 or genetic ablation of the NMDA receptor in these RGCs.

Results: To test the role of visual inputs on dendrite development, we dark-reared mice from P5 to P30 and found a modest effect on filopodia elimination in JamB RGCs. Anticipating that spontaneous glutamatergic activity in the retina may also contribute to RGC filopodia elimination, we blocked spontaneous glutamatergic activity by daily intraocular injections of AP5 and CNQX from P9 to P13. This led to an increase in filopodia density due to decreased dendrite length but no change in filopodia number. We confirmed this result by examining NMDAR knockout JamB cells (JamB-CreER:YFP:Grin1-/-). As expected, Grin1-/- JamB RGCs have decreased dendrite outgrowth like the pharmacologic blockade. However, filopodia elimination in these cells was significantly decreased as well, suggesting that NMDA and non-NMDA glutamate receptors might regulate the RGC dendritic development in a differential manner. This effect was dramatic at P13. To test if this effect persists into adulthood, we examined Grin1-/- JamB RGCs at P30 and found that they are indistinguishable from wild-type JamB RGCs, suggesting that a compensatory mechanism exists to drive dendrite elongation and filopodia elimination in the absence of the NMDA receptor.

Conclusions: Our study demonstrated that ganglion cell dendrite outgrowth and pruning of filopodia require glutamatergic activity and visual input that act via NMDA and possibly non-NMDA glutamate receptors.

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Abstract Human Retina

Human-color-retina

This image of ganglion cells, Müller cells and starburst amacrine cells in the human retina is from a patient suffering from retinitis pigmentosa (RP).  This disease this patient suffered from slowly causes people affected with this disease to go blind and is a constant reminder to me of why we engage in our research.

For some, this is a pretty, though abstract image created through a set of technologies called computational molecular phenotyping (CMP).   The colors in this image come from antibodies labeling taurine, glutamine and glutamate, all small molecular species that reveal metabolic states in these tissues.

For us, these images reveal variation in cell types as well as abnormalities in other kinds of cells that presage retinal stress and the cellular responses that alter the retina in ways that both cause blindness and make it difficult to rescue vision loss.  We also see the beginnings of changes in the circuitry of the retina that forever will alter the way that diseased retinas process information.

Image courtesy of Bryan William Jones, Ph.D. and originally appeared here.

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Full-Length Axon Regeneration In The Adult Mouse Optic Nerve and Partial Recovery of Simple Visual Behaviors

Friend of Webvision Yves Sauvé sent in this paper by Silmara de Lima, Yoshiki Koriyama, Takuji Kurimoto, Julia Teixeira Oliveira, Yuqin Yin, Yiqing Li, Hui-Ya Gilbert, Michela Fagiolini, Ana Maria Blanco Martinez, and Larry Benowitz that documents regeneration of the optic nerve in the adult mouse, a potentially substantial breakthrough in therapeutic recovery of vision lost through disease or trauma.

Continue reading “Full-Length Axon Regeneration In The Adult Mouse Optic Nerve and Partial Recovery of Simple Visual Behaviors”