First Author | Stark DT | Year | 2016 |
Journal | Invest Ophthalmol Vis Sci | Volume | 57 |
Issue | 15 | Pages | 6885-6894 |
PubMed ID | 28002563 | Mgi Jnum | J:258456 |
Mgi Id | MGI:6112231 | Doi | 10.1167/iovs.16-20748 |
Citation | Stark DT, et al. (2016) Subcellular Localization of a 2-Arachidonoyl Glycerol Signaling Cassette in Retinal Ganglion Cell Axonal Growth In Vitro. Invest Ophthalmol Vis Sci 57(15):6885-6894 |
abstractText | Purpose: To investigate whether the subcellular distribution of endocannabinoid (eCB) system (ECS) components in growing RGC axons is consistent with the formation of eCB-enriched "hotspots" and the role of the ECS in RGC axonal growth. Methods: We used immunocytochemistry and image analysis to quantify axonal expression of the ECS components diacylglycerol lipase alpha (DGLalpha), monoacylglycerol lipase (MGL), and cannabinoid receptor type 1 (CB1R) in a mouse retinal explant model. We tested whether pharmacologic antagonists of CB1R and inhibitors of eCB degradation modulate ECS component expression and axonal growth. Results: DGLalpha expression was higher in the distal RGC axon than in the growth cone central domain (GCCD) (95% confidence interval [CI], 106.5%-122.4% at 15 mum proximal to the GCCD), whereas MGL expression in the same region was not significantly different (95% CI, 88.8%-102.1%). In more proximal axon segments, DGLalpha and MGL expression were both lower than in the GCCD, whereas CB1R expression was 2.5-fold higher in this region (95% CI, 220.3%-278.4% at 50 mum proximal to the GCCD). The presence of CB1R antagonist O-2050 disrupted profiles of ECS component expression and increased axonal growth (95% CI for the difference of median axon lengths 26.6-55.6 muM). Conclusions: Our results demonstrate an ECS topology in RGC axons that is consistent with formation of eCB-enriched hotspots and suggest that the ECS has a role in CB1R-dependent inhibition of RGC axonal growth in vitro. |