| Myopia is a common refractive error, and posing a risk of pathological changes. Most animals including humans are born with hyperopia. In the growth process formed emmetropia gradually. This process relies on vision. If this process lack of early visual experience, are eventually leading to myopia. Form deprivation myopia (FDM) is employing methods, such as suturing the eyelids, wearing translucent goggles dispersion lenses or to change the visual experience delete, changes in refraction and axial length of the experimental animals, then myopia happened. Since Wiesel built up form deprivation myopia successfully by sewing the eyelids of rhesus monkey in 1977 for the first time, the method to establish animal models of myopia in constant development and improvement. Previous studies showed that form deprivation myopia is a complex process of change that involved in variety of media and factors. Recent studies more and more focus on the function and changes of neurotransmitter in retinal. In these neurotransmitters, people gradually pay attention to the melatonin (MLT).Melatonin is a neuroendocrine hormone, the chemical known as N-acetyl -5-methoxy tryptamine, and it transformed from 5-hydroxytryptamine. Melatonin enter the frog melanoma cells can make the frog's skin color lighter, so called melatonin. In physiological conditions, the melatonin of human and other mammals and birds mainly from the pineal. But some other organizations can also synthesize a small amount of melatonin, such as the retina, intestine, vice lacrimal gland and so on. Pineal melatonin secretion was regular fluctuations in 24-hour, it means secretion increases during the night and reduce during the day. Circadian rhythms control the secretion rhythm by the suprachiasmatic nucleus rhythm (SCN).Melatonin receptors play a role mainly through melatonin receptors. At the end of the twentieth century, the International Union of Pharmacology meeting was held, in this meeting MLT receptors were divided into 3 subtypes, namely MT1, MT2, MT3; Human retina and most of the eye tissues have MT1, MT2. MLT not only has the ability to remove hydroxyl radicals, but also can inhibit the body nitric oxide (NO) over-production, protect of injury and inflammation. C-fos is a proto-oncogene, belong to the immediate-early gene class. In this study, we establish the guinea pig model of form deprivation myopia and inject different doses of exogenous MLT, and observe every group guinea pig's refractive error, axial length, and retinal MT1, iNOS and c-fos changes. Speculat the formation of exogenous MLT's role in the FDM.Material and MethodsTo forty seven-days-old healthy male multicolor guinea pigs. Defore the cycloplegic retinoscopy guinea pigs to exclude congenital myopia and other eye diseases. Covering guinea pig's right eye with semi-transparent goggle to establish FDM model, the left eye as the control eye. The 40 guinea pigs were randomly divided into 4 groups of 10 each. Group A:The control group, by intraperitoneal injection of saline 5 ml·kg-1; B, C, D groups were treated with intraperitoneal injection of exogenous MLT 5 mg·kg-1,10 mg·kg-1,20 mg·kg-1, every other day, continuous infusion for 8 weeks. After 8 weeks of the experiment, the axial length was measured with A-mode ultrasound, the eyes refractive state was determined by streak retinoscopy, melatonin receptor MT1,iNOS and c-fos were analysed with immunohistochemistry. Imaging the retinal slice acquisition, analyze the protein expression by Image-Pro Plus 6.0 image analysis software, expressed of these indicators'intensity with the average optical density. All experimental data are denoted by x±s, using the SPSS 17.0 statistical package for data statistical analysis. First we test homogeneity of variance, then compar with univariate analysis of variance and LSD-t test, andα= 0.05 as the test standard. P<0.05 was considered statistically significant.Results1. In the FDM eyes of group A,the diopter,axial length,iNOS,MT1 and c-fos were (-7.86±0.26) D,(8.51±0.16) mm,(0.4836±0.0247),(0.3179±0.0344) and(0.2282±0.0246). Covered eye compared with the control eyes increased myopia, axial length growth, the immune activity of iNOS in the retina increased MT1, c-fos activity decreased (P<0.05).The FDM model was successfully established.2. Intra-peritoneal injection of different doses MLT, as compared with group A, these indexes were significantly inhibited or even reversed changes with doses of exogenous melatonin increased. In the FDM eyes of group C and D, the diopter,axial length,iNOS,MT1 and c-fos were (-4.30±0.59)and(-3.41±0.88)D,(8.04±0.24) and (7.43±0.39) mm,(0.3733±0.0427) and (0.3079±0.1261),(0.3743±0.0447) and (0.4055±0.0919),(0.3713±0.0786) and (0.4458±0.0974) respectively;Group C and Group D covered with the control group A have significant difference (P<0.05), the difference was statistically significant. Covered with group B and group A, the difference was not significant (P> 0.05).Conclusion1. Myopia of covered eye was increased and axial length was growthed after 8 weeks, the guinea pigs form deprivation myopia model has been successfully established.2. INOS expression in the retina of guinea pigs covered eye increased significantly, MT1, c-fos expression was significantly reduced, suggesting that iNOS, MT1 and c-fos may be involved in the formation of myopia.3. Exogenous melatonin can inhibit or even reverse the changes of refractive error, axial length and immunoreactivity of iNOS, MT1, c-fos in the FDM. 4. The high dose melatonin groups were more significant than the low dose group. Inferred on the basis, the exogenous melatonin may inhibited the formation of FDA. |
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