Retinal explants obtained from (cnr1+/+ or cnr1−/−) (A and B) or (cnr2+/+ or cnr2−/−) (C–E) embryos. In cnr1+/+ or cnr2+/+, administration of AM251, AM630, JTE907, and FSK increased growth cone surface area (A, C) and filopodia number (B, D) while ACEA, JWH015, and JWH133 decreased them. In cnr1−/−, responses of CB1R ligands (ACEA and AM251) were abolished (mean ± SEM; (A and B) n = 81 to 312 per condition, *P<0.05 vs control). In cnr2
−/− animals, growth cone surface area (C) and filopodia number (D) were only significantly modified by ACEA, AM251 and FSK while CB2R ligand (JWH015, JWH133, AM630, and JTE907) stimulation did not alter these endpoints (mean ± SEM; (C and D) n = 125 to 264 per condition, *P<0.05 vs control). (E) Growth cone surface area and filopodia number were increased in cnr2−/− compared to cnr2+/+. Mean ± SEM; n = 120 to 150 per condition, *P<0.05 vs control.