Study On Dopamine Transporter In Form Deprivation Myopia With Radiopharmaceutical Tracer

Form deprivation myopia（FDM） is one of the refractive errors in humans with identifiable causes such as neonatal eye closure,ptosis,corneal opacity,congenital cataract and eyelid haemangioma.Dopamine（DA）,as a neurotransmitter,is confirmed to be decreased in form deprivation myopia retina,which might contribute to the development of refractive errors induced by form deprivation.DAT regulates the effective concentration of extracellular DA and the changes in DAT may reflect those in extracellular DA concentration more directly.The purpose of this study was to investigate whether ^99mTc-TRODAT-1 Micro-SPECT（single-photon emission computed tomography） can image dopamine transporter（DAT） in form deprivation myopia retinas or not,and the feasibility of studying the changes of DAT in form deprivation myopia retinas with ^99mTc-TRODAT-1 Micro-SPECT.Our study established form deprivation myopia animal models,and performed the imaging of retinal DAT with Micro-SPECT and ex vivo autoradiography using ^99mTc-TRODAT-1.PartⅠ.Establishment and biometric measurement of FDM animal models.Purpose:To establish guinea pigs FDM animal models and observe the animal models whether to be successful or not through biometric measurement.Methods:Thirty healthy pigmented guinea pigs aged 3 weeks underwent biometric measurement（refraction and axial length） prior to the experiment,excluding congenital ametropia and eye diseases.Experimental animals were randomly assigned into two groups,groupⅠwas form deprivation myopia（FDM） group, monocularly-deprived goggles covering randomly for 4 weeks,and the untreated eyes served as self-controls.Pigmented guinea pigs in GroupⅡserved as normal controls. The same measurement went for both groups at the 4^th week,Twelve of the most successful models were chosen to enter our experiment finally,and there were both six animals in FDM group and normal control group respectively. Results:Following four weeks of form deprivation,all the deprived eyes became myopic,and axial length was longer compared with that of the fellow and normal control eyes.The refraction of fellow eyes,deprived eyes,and normal control eyes were 2.79±0.78 D,-3.17±0.98 D and 2.96±0.40 D respectively.Deprived eyes vs.fellow eyes（t = 13.549,P＜0.0001）,and deprived eyes vs.normal control eyes(F = 9.197,t = 14.132,P＜0.0001 o The axial length of fellow eyes,deprived eyes,and normal control eyes were 7.52±0.19 mm,7.90±0.19 mm and 7.51±0.15 mm respectively。Deprived eyes vs.fellow eyes（t = 13.549,P＜0.0001）, and deprived eyes vs.normal control eyes（F = 9.197,t = 14.132,P＜0.0001）。After form deprivation,deprived eyes had statistically significant differences compared with fellow eyes and normal control eyes.Conelusions:FDM animal models were successfully established,and could be used for further nuclide tracing study.PartⅡ.Study on dopamine transporter in retina with radiopharmaceutical tracerPurpose:To investigate whether ^99mTc-TRODAT-1 Micro-SPECT（single-photon emission computed tomography） can image dopamine transporter（DAT） in form deprivation myopia retinas or not,and the feasibility of studying the changes of DAT in form deprivation myopia retinas with ^99mTc-TRODAT-1 Micro-SPECT.Methods:After four weeks’ form deprivation,all the guinea pigs in FDM and normal control group were injected 740MBq ^99mTc-TRODAT-l（volume≤1ml）,and performed Micro-SPECT retina imaging one hour later,then decapitated and performed ex vivo autoradiography for half an hour,with Micro-CT and OptiQuant Acquisition & Analysis software analyzing retina region-of-interests（ROI）.Results:The retinas were clearly resolved with ^99mTc-TRODAT-1 in both Micro-SPECT imaging and ex vivo autoradiography.In Micro-SPECT imaging,the ratio of ^99mTc-TRODAT-1 uptake in the myopic retinas was 11.55±2.80,that in the normal control eyes was 15.20±1.98（P = 0.026,F = 2.94,t = 2.605）,and that in the fellow eyes was 13.90±2.04（P = 0.003,t = 5.476）.In ex vivo autoradiography,the ratio of ^99mTc-TRODAT-1 uptake in the myopic retina was 95.52±12.04,that in the normal control eyes was 114.06±7.81（P = 0.01,F = 0.331,t = 3.164）,and that in the fellow eyes was 112.47±15.67（P = 0.001,t = 7.179）.All the differences were statistically significant,and the results of Micro-SPECT were consistent with those of ex vivo autoradiography.Conclusions:^99mTc-TRODAT-1 Micro-SPECT retina imaging was clear,and it can trace the distributions and changes of DAT in retina.The difference of DAT in the retina between myopic eyes and normal control eyes or fellow eyes was significant. Radionuclide tracing may provide a new approach in vivo for further studies on the dopamine system in the myopia.