Yu Sun1,2, Ning Zhao2, Wangyuan Liu3, Miao Liu1, Zizhao Ju1, Jun Li1, Zhen Cheng4, Xingdang Liu5. 1. Department of Nuclear Medicine, Huashan Hospital, Fudan University, No.12 Urumchi Middle Road, Jing'an District, Shanghai, 200040, China. 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. 3. Department of Ophthalmology, Eye and ENT Hospital, Fudan University, No. 83 Fenyang Road, Xuhui District, Shanghai, 200031, China. 4. 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. zcheng@stanford.edu. 5. Department of Nuclear Medicine, Huashan Hospital, Fudan University, No.12 Urumchi Middle Road, Jing'an District, Shanghai, 200040, China. xingdliu@yahoo.com.
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.
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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