Morphine (MS) and VEGF promote proliferation and survival signaling in RECs of sickle mice, and MS-induced proliferation is dependent on MOR. (A) RECs from NY1DD sickle mice show concentration-dependent increase in proliferation by MS and VEGF. (B) MS (1 μM) and MOR-selective agonist DAMGO (1 μM) stimulated proliferation of RECs from NY1DD sickle mice, which was inhibited by nonselective antagonist naloxone (NAL; 1 μM) and MOR-selective antagonist CTOP (1 μM). Specific antagonists for opioid receptors δ (DPDPE; 1 μM) and κ (U50488H; 1 μM) had no effect on proliferation. N = 3 mice per treatment. All values are mean ± SEM, and significance (P < .01) was determined by 1-way analysis of variance, Dunnet’s multiple comparisons. (C) MS (10 μM) and VEGF₁₆₄ (100 ng/mL) promote survival signaling in NY1DD RECs. Results represent mean ± SEM of 3 independent experiments performed in triplicate. (D) N = 5 to 8 independent experiments. *P < .0005 vs phosphate-buffered saline (PBS) was determined by an unpaired 2-tailed t test, **P < .05 and ***P < .01 1-way analysis of variance with Bonferroni’s multiple comparisons.