| Abstract No.: | C-A3020 |
| Country: | Canada |
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| Title: | MODULATION OF RETINAL GANGLION CELL GROWTH BY PROTEIN KINASE A PATHWAY DURING DEVELOPMENT |
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| Authors/Affiliations: | 1 Anteneh Argaw*; 2 G. Duff; 4 D. Boire; 3 M. Ptito; 3 J-F Bouchard;
1 University of Montreal, Dept of Biomedical Science, Faculty of Medicine, School of Optometry, QC, Canada; 2 University of Montreal, Faculty of Pharmacy, QC, Canada; 3 University of Montreal, School of Optometry, QC, Canada; 4 UQTR, Departement of Chemistry-Biology, Trois-Rivičres, QC, Canada
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| Content: | During development, retinal ganglion cells (RGCs) extend their axons toward their specific targets in the thalamus and the superior colliculus. RGC axon navigation is largely directed by guidance cues present in their environment. cAMP has been proposed as an important second messenger during axon guidance and brain wiring in the developing central nervous system. Furthermore, it was reported that intracellular cAMP levels decrease significantly following birth in purified dorsal root ganglion cells and RGCs. In the present study, we tested if an early postnatal modulation of the cAMP/Protein Kinase A (PKA) pathway would affect RGC axon navigation. We observed a significant decline in retinal cAMP levels during early postnatal development. To investigate the effect of an increase in cAMP on retinal projection development, at postnatal day 1, hamsters received a unilateral injection of either 0.9% saline, 12mM of the membrane-permeable cAMP analogue dibutyryl cAMP, or 10µM of PKA inhibitor KT5720. Compared with the control group, intraocular elevation of cAMP significantly accelerated RGC growth whereas inhibition of PKA activity delayed axonal growth. When highly purified RGC cultures were treated with several pharmacological agents activating the cAMP/PKA pathway, neurite length, growth cone (GC) surface area and GC filopodia number were increased significantly. These effects were prevented by PKA inhibitors. Taken together, these results suggest that cAMP levels promote projection growth in part by directly modulating the PKA pathway in RGCs. Intraocular elevation of cAMP could potentially be an interesting route to promote retinal projection growth in pathological conditions particularly during early development.
This study was supported by NSERC grant to J.-F. B., A.A. is supported by a CNIB-CIHR studentship, J.-F. B. by a CIHR-Rx&D Scholar award, and M.P. holds the Harland Sanders Chair for Visual Science.
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