Zhang Lin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 68-86). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / TABLE OF CONTENTS --- p.ii / ABBREVIATIONS --- p.v / LIST OF TABLES --- p.vi / LIST OF FIGURES --- p.vii / Chapter 1. --- ABSTRACT (ENGLISH/CHINESE) --- p.1 / Chapter 2. --- INTRODUCTION --- p.6 / Chapter 3. --- LITERATURE REVIEW --- p.9 / Chapter 3.1. --- MYOPIA IN HUMAN --- p.9 / Chapter 3.1.1. --- Different types of myopia --- p.9 / Chapter 3.1.2. --- The pathologic change of myopia --- p.10 / Chapter 3.1.3. --- The prevalence of myopia --- p.13 / Chapter 3.1.4. --- Hereditary influence in human myopia --- p.13 / Chapter 3.1.5. --- Environmental influence in human myopia --- p.15 / Chapter 3.1.6. --- Nutrition in human myopia --- p.16 / Chapter 3.1.7. --- Pharmacological agents used to prevent progression of myopia --- p.16 / Chapter 3.1.8. --- Contact lens in the prevention of progression human myopia --- p.17 / Chapter 3.2. --- ANIMAL MODELS OF EXPERIMENTAL MYOPIA --- p.19 / Chapter 3.2.1. --- Experimental myopia in monkeys --- p.19 / Chapter 3.2.2. --- Experimental myopia in three shrew --- p.21 / Chapter 3.2.3. --- Experimental myopia in marmosets and guinea pigs --- p.23 / Chapter 3.2.4. --- Experimental myopia in chicks --- p.24 / Chapter 3.2.5. --- Summary --- p.26 / Chapter 3.3. --- PHARMACOLOGICAL STUDIES --- p.27 / Chapter 4. --- OBJECTIVES --- p.32 / Chapter 5. --- materials and methods --- p.34 / Chapter 5.1. --- ANIMALS AND INDUCTION OF FORM DEPRIVATION MYOPIA --- p.34 / Chapter 5.2. --- EYE GROWTH AND MYOPIC STUDY --- p.35 / Chapter 5.2.1. --- Refractive measurements --- p.35 / Chapter 5.2.2. --- Ultrasonographic measurements of eye size in vivo --- p.35 / Chapter 5.2.3. --- Measurements with calipers on enucleated eyes --- p.36 / Chapter 5.2.4. --- Weight of eye globes --- p.36 / Chapter 5.3. --- RETINAL CHANGE --- p.36 / Chapter 5.3.1. --- Light microscopy --- p.36 / Chapter 5.3.2. --- Calretinin immuno-reactivity study of the myopic retina --- p.37 / Chapter 5.4. --- DETECTION OF APOPTOTIC CELL DEATH --- p.38 / Chapter 5.4.1. --- TUNEL --- p.38 / Chapter 5.5. --- EFFECT OF RETINAL TOXINS ON MYOPIC EYES --- p.39 / Chapter 5.5.1. --- Intravitreal injection of iodoacetic acid (IAA) --- p.39 / Chapter 5.5.2. --- Intravitreal injection of glutamic acid --- p.40 / Chapter 5.5.3. --- "Intravitreal injection of 5,7-dihydrowytryptamine (5,7-DHT)" --- p.40 / Chapter 5.6. --- EFFECT OF LIGHTING ON MYOPIC EYES --- p.41 / Chapter 6. --- RESULTS --- p.42 / Chapter 6.1. --- REFRACTIVE STATES --- p.42 / Chapter 6.2. --- EYE SIZE MEASUREMENTS --- p.42 / Chapter 6.2.1. --- Ultrasonographic measurements in vivo --- p.42 / Chapter 6.2.2. --- Caliper measurements of chick eyes ex vivo --- p.43 / Chapter 6.3. --- WEIGHT OF EYE GLOBES --- p.45 / Chapter 6.4. --- RETINAL CHANGE --- p.45 / Chapter 6.4.1. --- Morphological features --- p.45 / Chapter 6.4.2. --- Morphometry of calretinin immuno-positive cells --- p.46 / Chapter 6.5. --- EFFECT OF RETINAL TOXINS ON MYOPIC EYE --- p.46 / Chapter 6.5.1. --- Intravitreal injection of iodoacetic acid (IAA) --- p.46 / Chapter 6.5.1.1. --- Eye growth measurements --- p.47 / Chapter 6.5.1.2. --- Retinal histological features --- p.47 / Chapter 6.5.2. --- Intravitreal injection of glutamic acid --- p.48 / Chapter 6.5.2.1. --- Eye growth measurements --- p.48 / Chapter 6.5.2.2. --- Retinal histological features --- p.49 / Chapter 6.5.3. --- "Intravitreal injection of 5,7,-dihydrowytryptamine (5,7-DHT)" --- p.50 / Chapter 6.5.3.1. --- Eye growth measurements --- p.50 / Chapter 6.5.3.2. --- Retinal histological features --- p.50 / Chapter 6.6. --- EFFECT OF LIGHTING ON MYOPIC EYES --- p.51 / Chapter 6.6.1. --- Eye growth measurements --- p.51 / Chapter 6.6.2. --- Retinal histological features --- p.51 / Chapter 7. --- DISCUSSION --- p.53 / Chapter 7.1. --- REFRACTIVE STATES --- p.55 / Chapter 7.2. --- CHANGE IN EYE SIZE --- p.56 / Chapter 7.2.1. --- The rate of eye growth --- p.56 / Chapter 7.2.2. --- Ultrasonographic measurements --- p.57 / Chapter 7.2.3. --- Axial length change with caliper measurements --- p.58 / Chapter 7.3. --- MORPHOLOGY AND MORPHOMETRY OF MYOPIC RETINA --- p.58 / Chapter 7.4. --- EFFECT OF RETINAL TOXINS ON MYOPIC EYES --- p.60 / Chapter 7.4.1. --- Intravitreal injection of iodoacetic acid --- p.60 / Chapter 7.4.2. --- Intravitreal injection of glutamic acid --- p.61 / Chapter 7.4.3. --- "Intravitreal injection of 5,7-DHT" --- p.63 / Chapter 7.5. --- EFFECT OF LIGHTING ON MYOPIC EYES --- p.64 / Chapter 8. --- CONCLUSION --- p.66 / BIBLIOGRAPHY --- p.68

In conclusion, the results suggested the important role of Ncl in driving the optic vesicle formation during early eye development. / The eye is a complex sense organ. It develops from different embryonic origins that including neural ectoderm, surface ectoderm, neural crest and paraxial mesoderm. Morphogenetic waves occur during eye development involve timely interactions of transcription factors and inductive signaling to ensure the correct temporal and spatial development of different components. Genetic studies of congenital eye defects, especially mutation screening and gene targeting, have provided the information about the molecular regulation in the complex processes of eye development. However, our knowledge of the basic genetic pathways that regulate the normal embryonic eye formation is incomplete. / Though the developing eye is believed to be highly specialized extension from the developing neural tube, the formation of major eye structure involves independent coordination of inductive interactions and regional specifications; formation of neural connections between retina and optic tectum; and maturation to a functional eye. There is not much information about eye-specific expression in early embryonic period. In this study, microarray was used to profile the molecular changes occurring in the developing mouse eye between the stage of optic vesicle evagination at E9.5 and completion of basic eye formation at P0. Differentially expressed transcription factor and signaling molecules, including nucleolin gene (Ncl), in the early developing eye were displayed. Temporal expression patterns were confirmed by quantitative real time PCR and spatial expressions patterns were confirmed by the whole-mount in situ hybridization. siRNA and overexpression vector targeting nucleolin transcript was designed to study their roles in the early eye morphogenesis during mouse embryogenesis in vitro. The loss of function phenotype after nucleolin knockdown was demonstrated by the absence of early optic vesicles with normal neural tube in the developing mouse embryos. Ectopic optic vesicle in developing mouse embryo was resulted under overexpression of Ncl . With the aim to study the biological roles of Ncl in mouse embryonic eye development in vivo, both conventional and conditional knockout techniques were attempted. The expression and functional studies revealed that a new neural tube independent signaling pathway regulated in the induction and formation of optic vesicles in the early eye formation. / Tang, Ling Yin. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3294. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 138-146). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Objetivo: Em anisométropes, comparar os valores médios individuais dos componentes oculares de ambos os olhos (poder da córnea, profundidade da câmara anterior, poder equivalente do cristalino e comprimento axial), correlacionar as diferenças dos componentes oculares com as diferenças de refração de ambos os olhos; verificar a contribuição total e a seqüência geral de influência das variáveis na diferença refrativa; e identificar o menor número de fatores que contenham o mesmo grau de informações expressas no conjunto de variáveis que influenciam na diferença refrativa. Métodos: Realizou-se um estudo transversal analítico em população de 77 anisométropes de duas ou mais dioptrias, atendida no ambulatório de Oftalmologia do Hospital Universitário da Faculdade de Medicina Nilton Lins, Manaus, Amazonas. Os anisométropes foram submetidos à refração estática objetiva e subjetiva, ceratometria e biometria ultra-sônica A-scan. A análise dos dados foi feita por meio dos seguintes modelos estatísticos: análise univariada, multivariada, de regressão múltipla e fatorial. Resultados: Não houve diferenças significativas na comparação dos valores médios individuais dos componentes oculares entre os olhos. Houve correlação negativa média entre a diferença refrativa e a diferença de comprimento axial (r=-0,64) (P<0,01) e correlação negativa fraca entre a diferença refrativa e a diferença de poder do cristalino (r=-0,34) (p<0,01). As variáveis analisadas responderam, no seu conjunto, por 78% da variação total para a diferença refrativa. A seqüência geral de influência das variáveis na diferença refrativa foi a seguinte: comprimento axial, poder do cristalino, poder da córnea e profundidade da câmara anterior. Foram identificados três fatores para a diferença refrativa: a) fator 1 (refração, comprimento axial); b) fator 2 (profundidade da câmera anterior, poder da córnea) e c) fator 3 (poder do cristalino). Conclusões: O estudo conduzido em 77 indivíduos com anisometropias variando de 2,00 a mais de 19,00 dioptrias, realizado para avaliar a influência dos componentes oculares, mostrou que o comprimento axial foi o principal fator causador das anisometropias, seguido pelo cristalino que contribuiu menos, depois pela córnea e profundidade da câmara anterior, com contribuições ainda menores. A investigação sugere falência no mecanismo adaptativo normal em anisometropia, o que poderia produzir não só descontrole do alongamento do comprimento axial (fator 1), mas também falência no controle do aplanamento da córnea e do aprofundamento da câmara anterior (fator 2) e no achatamento do cristalino (fator 3). / Purpose: To compare the individual means of ocular components of both eyes (corneal power, anterior chamber depth, crystalline lens power and axial length) in patients with anisometropia; to correlate the differences of the ocular components with refractive differences in both eyes; to verify total contribution and the sequence of influence that variables have in refractive differences, and to identify the smallest number of factors that contain the same level of information expressed in the set of variables that influence refractive difference. Methods: An analytical transversal study was carried out in 77 patients with anisometropia of two or more dioptres seen at the Ophthalmologic Clinic, University Hospital, Medical School Nilton Lins, Manaus, Amazon state. All participants were submitted to ophthalmologic exam which included objective and subjective cycloplegic refractometry, keratometry and ultrasonic biometry. Data analysis comprised the following statistical models: univariate, multivariate, multiple and factorial regression analyses. Results: There were no significant differences in the comparison of the individual means of the ocular components. There was negative correlation between refractive difference and difference of axial length (r=- 0.64; p<0.01) and weak negative correlation between refractive difference and crystalline lens power difference (r=-0.34; p< 0.01). The analyzed variables amounted to 78% of the total variation of refractive difference. The general sequence of variables influencing refractive difference was: axial length, crystalline lens power, cornea power, and anterior chamber depth. There were three factors identified for refractive differences: a) factor 1 (refraction, axial length); b) factor 2 (anterior chamber depth, cornea power), and c) factor 3 (crystalline lens power). Conclusions: Seventy-seven cases of anisometropia ranging from 2,00 to over 19,00 dioptres, examined for the individual components of refraction, showed that axial length was the major causative factor; crystalline lens have contributed less, followed by cornea and anterior chamber length. This study has suggested deficit of the normal adaptive mechanism in anisometropia that could produce not only axial elongation (factor 1), but also failure to control flattening of the cornea, deepening of the anterior chamber length (factor 2) and flattening of crystalline lens (factor 3).

Objetivo: Em anisométropes, comparar os valores médios individuais dos componentes oculares de ambos os olhos (poder da córnea, profundidade da câmara anterior, poder equivalente do cristalino e comprimento axial), correlacionar as diferenças dos componentes oculares com as diferenças de refração de ambos os olhos; verificar a contribuição total e a seqüência geral de influência das variáveis na diferença refrativa; e identificar o menor número de fatores que contenham o mesmo grau de informações expressas no conjunto de variáveis que influenciam na diferença refrativa. Métodos: Realizou-se um estudo transversal analítico em população de 77 anisométropes de duas ou mais dioptrias, atendida no ambulatório de Oftalmologia do Hospital Universitário da Faculdade de Medicina Nilton Lins, Manaus, Amazonas. Os anisométropes foram submetidos à refração estática objetiva e subjetiva, ceratometria e biometria ultra-sônica A-scan. A análise dos dados foi feita por meio dos seguintes modelos estatísticos: análise univariada, multivariada, de regressão múltipla e fatorial. Resultados: Não houve diferenças significativas na comparação dos valores médios individuais dos componentes oculares entre os olhos. Houve correlação negativa média entre a diferença refrativa e a diferença de comprimento axial (r=-0,64) (P<0,01) e correlação negativa fraca entre a diferença refrativa e a diferença de poder do cristalino (r=-0,34) (p<0,01). As variáveis analisadas responderam, no seu conjunto, por 78% da variação total para a diferença refrativa. A seqüência geral de influência das variáveis na diferença refrativa foi a seguinte: comprimento axial, poder do cristalino, poder da córnea e profundidade da câmara anterior. Foram identificados três fatores para a diferença refrativa: a) fator 1 (refração, comprimento axial); b) fator 2 (profundidade da câmera anterior, poder da córnea) e c) fator 3 (poder do cristalino). Conclusões: O estudo conduzido em 77 indivíduos com anisometropias variando de 2,00 a mais de 19,00 dioptrias, realizado para avaliar a influência dos componentes oculares, mostrou que o comprimento axial foi o principal fator causador das anisometropias, seguido pelo cristalino que contribuiu menos, depois pela córnea e profundidade da câmara anterior, com contribuições ainda menores. A investigação sugere falência no mecanismo adaptativo normal em anisometropia, o que poderia produzir não só descontrole do alongamento do comprimento axial (fator 1), mas também falência no controle do aplanamento da córnea e do aprofundamento da câmara anterior (fator 2) e no achatamento do cristalino (fator 3). / Purpose: To compare the individual means of ocular components of both eyes (corneal power, anterior chamber depth, crystalline lens power and axial length) in patients with anisometropia; to correlate the differences of the ocular components with refractive differences in both eyes; to verify total contribution and the sequence of influence that variables have in refractive differences, and to identify the smallest number of factors that contain the same level of information expressed in the set of variables that influence refractive difference. Methods: An analytical transversal study was carried out in 77 patients with anisometropia of two or more dioptres seen at the Ophthalmologic Clinic, University Hospital, Medical School Nilton Lins, Manaus, Amazon state. All participants were submitted to ophthalmologic exam which included objective and subjective cycloplegic refractometry, keratometry and ultrasonic biometry. Data analysis comprised the following statistical models: univariate, multivariate, multiple and factorial regression analyses. Results: There were no significant differences in the comparison of the individual means of the ocular components. There was negative correlation between refractive difference and difference of axial length (r=- 0.64; p<0.01) and weak negative correlation between refractive difference and crystalline lens power difference (r=-0.34; p< 0.01). The analyzed variables amounted to 78% of the total variation of refractive difference. The general sequence of variables influencing refractive difference was: axial length, crystalline lens power, cornea power, and anterior chamber depth. There were three factors identified for refractive differences: a) factor 1 (refraction, axial length); b) factor 2 (anterior chamber depth, cornea power), and c) factor 3 (crystalline lens power). Conclusions: Seventy-seven cases of anisometropia ranging from 2,00 to over 19,00 dioptres, examined for the individual components of refraction, showed that axial length was the major causative factor; crystalline lens have contributed less, followed by cornea and anterior chamber length. This study has suggested deficit of the normal adaptive mechanism in anisometropia that could produce not only axial elongation (factor 1), but also failure to control flattening of the cornea, deepening of the anterior chamber length (factor 2) and flattening of crystalline lens (factor 3).