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

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.

• Authors: Yu Sun, Ning Zhao, Wangyuan Liu, Miao Liu, Zizhao Ju, Jun Li, Zhen Cheng, Xingdang Liu
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 20 Issue 5 Pg. 771-779 (10 2018) ISSN: 1860-2002 [Electronic] United States
• PMID: 29520623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorine Radioisotopes
• Vesicular Monoamine Transport Proteins
• 3,4-Dihydroxyphenylacetic Acid
• florbenazine F 18
• Dopamine
• Homovanillic Acid
• Tetrabenazine

Topics

• 3,4-Dihydroxyphenylacetic Acid (chemistry)
• Animals
• Dopamine (metabolism)
• Fluorine Radioisotopes (chemistry)
• Guinea Pigs
• Homovanillic Acid (chemistry)
• Myopia (diagnostic imaging, metabolism, pathology)
• Positron Emission Tomography Computed Tomography
• Refractive Errors (diagnostic imaging, metabolism, pathology)
• Retina (diagnostic imaging, metabolism, pathology)
• Tetrabenazine (analogs & derivatives, chemistry)
• Vesicular Monoamine Transport Proteins (metabolism)