| Myopia is the most common eye disorder worldwide. By now, the etiology and pathogenesis of myopia are not clear, so we have not effective measures for prevention and treatment. This is the hot point of the optical study. Many kinds of animals such as chick, monkey and tree shrew can be induced myopia by form deprivation such as suture of eyelid, cornea blur, translucent goggles and negative lens. Constructions of animal model of myopia are very necessary for exploring the etiology and pathogenesis of myopia. Form deprivation myopia has great differences with human myopia. Lens-induced myopias have much similarities with human myopia. In the past , high degree lens were used to cause significant hyperopic or myopic defocus , and the changes of animal's refractive state were observed. The study on low degree lens induction has not been reported. Low-degree lens induction cause mild defocus, and this kind of mini-changes is much similar to the state of human eye when they see the near objects or when the myopias are over-corrected. So this kind of study could help us to know the pathogenesis of refractive errors. In our study, we first designed the high and low-degree lens according to the real diopters of guinea pigs, and explored the sensitivity of guinea pigs to lens-induction.Enlargement of eyeball and scleral remolding are the main changes of myopia. Sclera plays a important role in regulation of eye development. In experimental myopia and human myopia, we can find abnormal expression of gene for extracellular matrix and changes of ECM and collogen fibers in sclera. By now, the changes ofscleral matrix and growth factors have been reported in chick, tree shrew and rhesus monkey form deprivation myopias. But the similar studies on len-induced myopia of guinea pig have not been reported. We observed the changes of scleral matrix and growth factors in lens-induced myopia of guinea pigs, and explored the differences of pathogenesis of lens-induced myopia and form-deprivation myopia.Part 1 THE STUDY OF REFRACTIVE CHANGES OF GUINEAPIG BY LENS INDUCTIONObjective: The young guinea pigs wore positive or negative lens of different diopter to disturb visual development and induce myopic or hyperopic defocus. The changes of refractive state and the sensitivities of guinea pigs to defocus were observed.Method: According to the real refraction of every animal, we designed the different concave and convex. All the animals were devided into seven groups, including group A(no interference), group B(wearing the completely corrected convex), group C (wearing the positive lens lower 2D than the real diopter), group D (wearing -3D concave), group E (wearing -6D concave), group F (wearing -10D concave), group G(wearing +6D convex). Before and after experiments, the axial lengths and refractive states were detected by A scan and retinoscopy.Result: Myopias of -3.32±1.07D and -3.43±0.24D were induced in group E and group F, and the axial lengths prolonged for 0.42±0.11mm and 0.36±0.19mm in these two groups. Hyperopia of 4.28±2.20D was induced in group G, and having statistical difference when being compared with contrast eyes, but the axial lengths had not the significant changes. In group B, complete correction made the guinea pig' eyes being emmetropization, so no obvious changes of diopter and axial lengths for induced eyes occured after experiment, but the diopter of contrast eye decreased obviously. After experiment, group C reserved 1.80±0.48D hyperopias and had statistical differencescomparing with contrast eyes(0.45±0.72D). For induced eyes, the changeable values of diopter were 2.20±0.48D, similar to 2D(p>0.05). Group D had not induced myopias, the diopter were 0.30±2.17D, changes of diopter and axial lengths had no statistical significances.Conclusion: The positive and negative lens can successfully induce guinea pig eye to form the model of myopia and hyperopia. The dioper of induced lens has positive correlation with post-experiment diopter, and the higher the lens-induced diopter, the better the result. The high-degree concave and convex can cause guinea pig eyes to form myopia or hyperopia because of hyperopic or myopic defocus. The low-degree positive lens can cause refractive changes of guinea pigs. The low-degree negative lens cannot induce myopias. When hyperopias of guinea pigs are corrected completely, the changes of diopters become slowly. The positive lens which degrees are lower than the real diopters cause mild hyperopic defocus and the value of changed diopter is nearer to the differences between induced lens and real diopters of guinea pigs. The vision-induced emmetropization in a most degree control the development of diopter myopia from origin. It suggests that guinea pigs are sensitive to hyperopic and myopic defocuses caused by concave and convex. The environmental factors can interfere development of vision and induce changes in refraction. So active emmetropization induced by vision play a great role in controlling the developments of eyeball lengths and refractions.PART 2 THE STUDY OF THE ROLE OF MMP-2 AND TIMP-2 IN LENS-INDUCED MYOPIC SCLERAObjective: To study the role of MMP-2 and TIMP-2 in lens-induced myopic sclera of guinea pigs.Method: 11 guinea pigs which were successfully induced myopias were extracted eyeballs, and the scleras near posterior poles were observed byimmunohistochemistry methods. The positive rates of MMP-2 and TIMP-2 in scleral fibroblast cytoplasma and the area percentageratio of positive cells were calculated and contrasted to controlled eyes.Result: The results were that the positive rate of MMP-2 in myopic sclera of guinea pigs was 81.8%, higher than contrast eyes(45.5%); the positive rate of TIMP-2 was 36.4%, lower than the contrast eyes(72.7%). The area percentage ratio of MMP-2 positive cells of myopic eyes was 0.22 + 0.15, significantly higher than contrast eyes (0.06 ±0.08) . The ratio of TIMP-2 positive cells in myopic eyes was 0.05 + 0. 08, lower than contrast eyes (0.13 + 0. 10) .Conclusion: In lens-induced experimental myopias of guinea pigs, increasing of MMP-2 and decreasing of TIMP-2 occur in posterior scleral matrix. This pair of disbalance of MMP-2 and TIMP-2 can cause abnormal growth of guinea pig's eyeball. These changes in lens-induced myopias are the same as form deprivation myopia. So, that means lens-induced myopia and form deprivation myopia have partially the same regulating mechanism in myopic scleral changes.PART 3 THE STUDY OF THE ROLE OF TGF-fc ANDBFGF IN LENS-INDUCED MYOPIC SCLERAObjective: To study the role of TGF-P2 and bFGF in lens-induced myopic sclera of guinea pigs.Method: 11 guinea pigs which were successfully induced myopias were extracted eyeballs, and the scleras near posterior poles were observed by immunohistochemistry methods. The positive rates of TGF-f}2 and bFGF in scleral fibroblast cytoplasma and the area percentageratio of positive cells were calculated and contrasted to controlled eyes.Result: The results were that the positive rate of TGF-(32 in myopic sclera of guinea pigs was 81.8%, higher than contrast eyes(36.4%); the positive rate of bFGF...
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