Retinal image properties such as contrast and spatial frequency play important roles in the development of normal vision. For example, visual environments comprised solely of low contrast and/or low spatial frequencies induce myopia. The visual image is processed by the retina and it then locally controls eye growth. In terms of the retinal neurotransmitters that link visual stimuli to eye growth, there is strong evidence to suggest involvement of the retinal dopamine (DA) system. For example, effectively increasing retinal DA levels by using DA agonists can suppress the development of form-deprivation myopia (FDM). However, whether visual feedback controls eye growth by modulating retinal DA release, and/or some other factors, is still being elucidated. This thesis is chiefly concerned with the relationship between the dopaminergic system and retinal image properties in eye growth control. More specifically, whether the amount of retinal DA release reduces as the complexity of the image degrades was determined. For example, we investigated whether the level of retinal DA release decreased as image contrast decreased. In addition, the effects of spatial frequency, spatial energy distribution slope, and spatial phase on retinal DA release and eye growth were examined. When chicks were 8-days-old, a cone-lens imaging system was applied monocularly (+30 D, 3.3 cm cone). A short-term treatment period (6 hr) and a longer-term treatment period (4.5 days) were used. The short-term treatment tests for the acute reduction in DA release by the visual stimulus, as is seen with diffusers and lenses, whereas the 4.5 day point tests for reduction in DA release after more prolonged exposure to the visual stimulus. In the contrast study, 1.35 cyc/deg square wave grating targets of 95%, 67%, 45%, 12% or 4.2% contrast were used. Blank (0% contrast) targets were included for comparison. In the spatial frequency study, both sine and square wave grating targets with either 0.017 cyc/deg and 0.13 cyc/deg fundamental spatial frequencies and 95% contrast were used. In the spectral slope study, 30% root-mean-squared (RMS) contrast fractal noise targets with spectral fall-off of 1/f0.5, 1/f and 1/f2 were used. In the spatial alignment study, a structured Maltese cross (MX) target, a structured circular patterned (C) target and the scrambled versions of these two targets (SMX and SC) were used. Each treatment group comprised 6 chicks for ocular biometry (refraction and ocular dimension measurement) and 4 for analysis of retinal DA release. Vitreal dihydroxyphenylacetic acid (DOPAC) was analysed through ion-paired reversed phase high performance liquid chromatography with electrochemical detection (HPLC-ED), as a measure of retinal DA release. For the comparison between retinal DA release and eye growth, large reductions in retinal DA release possibly due to the decreased light level inside the cone-lens imaging system were observed across all treated eyes while only those exposed to low contrast, low spatial frequency sine wave grating, 1/f2, C and SC targets had myopic shifts in refraction. Amongst these treatment groups, no acute effect was observed and longer-term effects were only found in the low contrast and 1/f2 groups. These findings suggest that retinal DA release does not causally link visual stimuli properties to eye growth, and these target induced changes in refractive development are not dependent on the level of retinal DA release. Retinal dopaminergic cells might be affected indirectly via other retinal cells that immediately respond to changes in the image contrast of the retinal image.

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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

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The goal of my doctoral work is to understand how proteins involved in vesicle trafficking contribute to proper animal development. To understand aspects of this process, I studied how two vesicle trafficking proteins, Liquid facets(Lqf)/epsin1 and D-Epsin-Related, affect Drosophila eye development. I determined that Lqf, an endocytosis protein, together with Fat facets (Faf), a deubiquitinating enzyme, regulate the Notch and Delta signaling in the developing Drosophila eye. Notch signaling pathway is used in most developmental processes and is dependent on its ligand Delta. Faf deubiquitinates Lqf in the signaling cells, thereby increasing Lqf protein levels and also levels of Delta endocytosis. This event is necessary for Notch activation in neighboring cells. Lqf probably works in concert with the E3 ubiquitin ligase Neuralized (Neur), which ubiquitinates Delta. These conclusions are consistent with a relatively new model describing an obligate role for endocytosis in the signaling cells to effect activation in neighboring cells. To understand how Lqf functions mechanistically in this process, I performed a structure/function analysis of the Lqf protein. Lqf proteins with strategic deletions of certain functional domains were tested for their ability to function in vivo. The major result of these experiments is that the N-terminal ENTH domain of Lqf and a protein without the ENTH domain each retain significant activity. This suggests that Lqf has two functions: the ENTH domain function and the ENTH-less function. These data are in contrast with the most popular model suggesting that ENTH-less epsins are non-functional proteins. I present possible models for how ENTH-less epsins may retain function. The final part of my thesis focuses on D-Epsin-Related (D-Epsin-R) protein. I showed that D-Epsin-R is a Golgi protein, like its homologs. Surprisingly, D-Epsin-R ENTH domain is not required for function because an ENTH-less D-Epsin-R can substitute for endogenous D-Epsin-R. Also, D-Epsin-R has essential and probably specific developmental roles in the eye as D-Epsin-R mutants exhibit impaired cell growth. This work suggests that epsins are specific components of certain developmental pathways. / text

No description available.

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.

Die Arbeit umreißt das Krankheitsbild der Myopie (Kurzsichtigkeit) und deren unterschiedliche Ausprägungen, im Speziellen der progressiven und pathologischen Myopie. Hierbei wird ein Einblick in die Symptomatik, die anatomischen Ursachen und die heutigen medizinischen Interventionen gegeben. Hierdurch wird die Problematik einer zu „weichen“ Sklera (Lederhaut des Auges) und des damit einhergehenden fortschreitenden Augenwachstums deutlich. Im Zentrum der Arbeit steht ein neuer therapeutischer Ansatz zur vorbeugenden Behandlung der pathologischen Myopie; das Riboflavin/Blaulicht Cross-Linking der Sklera des Kaninchenauges. Dessen Wirkungsweise ermöglicht die biomechanische Versteifung von kollagenem Gewebe. Aus diesem Sachverhalt ergibt sich die Fragestellung der Arbeit: Ist das sklerale Riboflavin/Blaulicht Cross Linking geeignet das Augenwachstum im Tiermodell (junge Kaninchen) verträglich zu hemmen? Operationsbeeinflussende Parameter wie die Riboflavin-Durchdringungsdauer der Sklera und die sklerale Lichtdurchlässigkeit werden untersucht und für die Optimierung der Operationsmethode herangezogen und diskutiert. Zur Einschätzung des Versuchsansatzes werden die im Methodikteil dargelegten Anwendungen an adulten und jungen Kaninchen/Kaninchenaugen durchgeführt. In Tierversuchen wird die Schadensschwelle in Abhängigkeit der Blaulichtintensität, des Alters und der Pigmentierung untersucht, wobei histologische, immunhistochemische und elektronenmikroskopische Verfahren angewendet werden. Der inhibitorische Einfluss des Riboflavin/Blaulicht Cross-Linkings auf das Augenwachstum kann im Jungtiermodell durch verschiedene metrische Verfahren und MRT-Untersuchungen belegt werden.

In eukaryotes, the process of nuclear migration is critical in fusion of haploid pronuclei after fertilization, in separation of daughter nuclei during mitosis, and in nuclear positioning in interphase cells. Experiments in several organisms have identified the basic protein requirements for nuclear migration and positioning: molecular motors that provide motive force; the cytoskeleton along which motors move nuclei, or to which the nuclei are anchored; and proteins of the outer and inner nuclear envelopes. These nuclear membrane proteins interact with the motors, the nuclear lamina and each other to effect nuclear migration and positioning. Proteins containing a SUN domain, which were first characterized in S. pombe Sad1 and C. elegans UNC-84, are inner nuclear envelope linkers of the nucleus to the cytoskeleton. In fungi, C. elegans, D. discoideum and vertebrates, these proteins are required not only for nuclear positioning, but also for maintaining the connection of the nucleus to the MTOC, for centrosomal duplication, for homologous pairing of chromosomes in meiosis, for distribution of nuclear pore complexes and for connecting the centrosome to chromatin to ensure genomic stability. The D. melanogaster genome has two genes, CG18584 and CG6589, which encode SUN domain proteins. The specific aims of my dissertation research were to generate null mutants in these genes, to characterize their null phenotypes, and to analyze where the genes are expressed. CG18584 = klaroid mutants are grossly normal, but adult eyes are mildly rough due to a defect in nuclear positioning that occurs during larval eye development. Klaroid protein is perinuclear in every cell of the eye, and functions by localizing the MTOC connector Klarsicht to the outer nuclear envelope. CG6589 = dspag4 null mutants are male sterile. In mature sperm, Dspag4 protein localizes rostrally to the sperm centriole. In the absence of Dspag4, most steps of gametogenesis occur normally, however, prior to the final steps of sperm maturation, the sperm nucleus dissociates from its centriole. Klaroid and Dspag4 thus have cellular roles typical for SUN domain proteins, and Dspag4 is unique in that its function is to attach nuclei to centrioles exclusively in maturing spermatids in the male germline. / text

No description available.