Abstract: Objective: To determine if the loss of function of retinal vasoactive intestinal peptide receptor 2 (Vipr2) affects dopamine (DA) turnover and retinal electrophysiology behavior. Methods: This is an experimental study. RT-PCR analyzed vasoactive intestinal peptide (Vip) and Vipr2 mRNA expression levels in different ocular tissues of 4- week-old male wildtype C57BL/6J mice. CRISPR-Cas9 gene-editing technology constructed the Vipr2-KO mice. Their refraction, turnover of retinal dopamine, and electroretinograms were measured and compared in these two different groups of 4-week-old Vipr2-KO and Vipr2-WT mice. Statistical analysis of the refraction and DA turnover used the independent sample t-test, and the data of retinal electrophysiology were evaluated with the two-way repeated measures ANOVA between these two different groups of mice. Results: Vip and Vipr2 mRNA levels were highly expressed in the retina, choroid/ retinal pigment cells, cornea, and sclera. In the iris and lens, Vipr2 mRNA was expressed at very low levels whereas the Vip mRNA expression level was undetectable. The refraction of 4-week-old Vipr2-KO mice was significantly shifted more towards myopia than that in the Vipr2-WT mice (t=2.51, P=0.017). The contents of DA, 3, 4-dihydroxyphenylacetate (DOPAC), and homovanillic acid (HVA) were significantly increased more in the 4-week-old Vipr2-KO mice than in the Vipr2-WT mice (t=3.42, P=0.001; t=2.15, P=0.037; t=3.27, P=0.002, respectively). However, the levels of DA, DOPAC, DOPAC/DA, HVA, and norepinephrine in the vitreous humor were not altered between these two different groups. The amino acid contents of aspartic acid, glutamic acid, serine, glutamine, glycine, taurine, and γ-aminobutyric acid were invariant in the retina and vitreous humor of these groups. The b-wave amplitudes under scotopic conditions (-3.699, -2.201, -0.699, 0.301, 0.799 log cd·s/m2 ) were higher in the 4-week-old Vipr2- KO mice than in its Vipr2-WT counterpart (F=8.65, P=0.015). Conclusions: Loss of Vipr2 function induces a refractive shift towards myopia at age 4 weeks, and alters both the retinal DA turnover and electroretinogram pattern. These changes suggest that loss of Vipr2 function alters retinal function and is thereby involved in myopia progression, but its mode of action requires further study.
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