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Study of Vesicular Monoamine Transporter 2 in Myopic Retina Using [18F]FP-(+)-DTBZ

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Abstract

Purpose

To investigate the relationship between expression level of vesicular monoamine transporter 2 (VMAT2) and myopia, as well as the feasibility of noninvasive myopia diagnosis through imaging VMAT2 in retina by using [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ).

Procedures

The right eyes of ten guinea pigs were deprived of vision to establish form-deprived (FD) myopia and the left eyes were untreated as the self-control eyes. The location and expression level of VMAT2 in the eyes were detected by micro-positron emission tomography (PET)/X-ray computed tomography (CT) imaging through using [18F]FP-(+)-DTBZ. Immunofluorescence staining and Western blot were used to confirm the location and expression level of VMAT2 in the eyes. The concentrations of dopamine (DA) and its metabolites including 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were also investigated by high-performance liquid chromatography.

Results

The right eyes deprived of vision were obviously myopic (− 3.17 ± 1.33 D) after procedure, while the left eyes were hyperopic (4.60 ± 0.83 D, P < 0.0001). The main expressions of VMAT2 in the eyes were located in retina. VMAT2 was significantly reduced in the myopic retina compared to the normal one from PET/CT results (P = 0.0008), which could also be verified by Western blots (P = 0.029). The concentrations of DA, DOPAC, and HVA in the FD eyes were all significantly less than those in the control eyes (P = 0.024, P = 0.018, P = 0.008). As a role of storing and releasing DA in vesicles, VMAT2 was demonstrated positively correlating with the amounts of DA (P = 0.030), DOPAC (P = 0.038), and HVA (P = 0.025) through Pearson’s correlation coefficient test.

Conclusions

We demonstrate that [18F]FP-(+)-DTBZ can be used to noninvasively image VMAT2 in retina. The expression level of VMAT2 in retina may act as a new biomarker for myopia diagnosis. The decreasing of VMAT2 expression level may play an important role in the development of myopia through correspondingly reducing the amount of DA in retina.

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Acknowledgements

We thank Dr. Jinhui Dai from Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China.

Funding

This work was supported by National Natural Science Foundation of China (Grant 81571706).

Author information

Author notes

  1. Yu Sun and Ning Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Huashan Hospital, Fudan University, No.12 Urumchi Middle Road, Jing’an District, Shanghai, 200040, China

    Yu Sun, Miao Liu, Zizhao Ju, Jun Li & Xingdang Liu

  2. Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University, 1201 Welch Road, Lucas Center, Palo Alto, CA, 94305, USA

    Yu Sun, Ning Zhao & Zhen Cheng

  3. Department of Ophthalmology, Eye and ENT Hospital, Fudan University, No. 83 Fenyang Road, Xuhui District, Shanghai, 200031, China

    Wangyuan Liu

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  1. Yu Sun
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  2. Ning Zhao
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  4. Miao Liu
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Corresponding authors

Correspondence to Zhen Cheng or Xingdang Liu.

Ethics declarations

All experiment procedures were approved by the Administrative Panel on Laboratory Animal Care (APALC) at Huashan Hospital, Fudan University.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Sun, Y., Zhao, N., Liu, W. et al. Study of Vesicular Monoamine Transporter 2 in Myopic Retina Using [18F]FP-(+)-DTBZ. Mol Imaging Biol 20, 771–779 (2018). https://doi.org/10.1007/s11307-018-1183-1

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  • DOI: https://doi.org/10.1007/s11307-018-1183-1

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