Objective: To investigate the effect of reduced extracellular dopamine (DA) levels on refractive development in guinea pigs by periocularly injecting a noncompetitive vesicular monoamine transporter 2 (VMAT2) antagonist, tetrabenazine (TBZ). Methods: Three-week-old guinea pigs were randomly divided into 8 groups in this experimental group. Seventy-eight animals were raised under normal vision (NV) and divided into the following groups: the normal control (NC, n=18), vehicle (dimethyl sulfoxide,NV+DMSO, n=18), low-dose TBZ (NV+30 ng, n=22), and high-dose TBZ (NV+300ng, n=20) groups.Seventy-four animals raised with form deprivation (FD) were divided into the following groups: FD (n=17),FD+DMSO (n=18), FD+30 ng (n=21) and FD+300 ng (n=18) groups. DMSO, TBZ (30 ng or 300 ng) was periocularly injected into the right eyes daily in 100 µl of 0.1% DMSO. Refractive changes were evaluated prior to treatment and 2 weeks and 4 weeks after treatments. p-CREB immunofluorescent staining evaluated DA receptor activation. Data were analyzed using one-way ANOVA and an independent samples
t-test. Results: After 2 weeks of TBZ injections, guinea pigs developed myopia in the NV environment.The inter-ocular difference in refraction for NV+DMSO, NV+30 ng and NV+300 ng were 0.04 ± 0.31 D,-0.90 ± 0.84 D and -0.75 ± 0.66 D, respectively (F=11.133, P < 0.001). The vitreous chamber depth in these three groups was increased consistently with the inter-ocular differences of -0.01 ± 0.03 mm,0.02 ± 0.03 mm and 0.02 ± 0.04 mm (F=6.001, P=0.004). Four weeks of TBZ injection could not further increase myopia. The inter-ocular differences between NV+DMSO, NV+30 ng and NV+300 ng were -0.06 ± 0.41 D, -1.14 ± 1.61 D and -0.84 ± 1.41 D, respectively (F=3.569, P=0.035). Four weeks of TBZ application significantly reduced the number of cells that expressed p-CREB in the retinal ganglion cell layer and inner nuclear layer (t=4.825, P=0.003, t=8.109, P < 0.001). TBZ injections did not affect the development of form deprivation myopia (FDM) in guinea pigs. Conclusions: The VMAT2 function inhibition by TBZ induces myopia in guinea pigs raised in NV but does not affect the development of FDM. This effect might be mediated by a reduced release of monoamine transmitters, especially DA.