Myocilin, expressed in the trabecular meshwork of the eye, has been linked to inherited primary open-angle glaucoma (POAG). The biological function of myocilin is unknown, but mutant myocilin exhibits a gain-of-function mechanism, aggregating within the endoplasmic reticulum of human trabecular meshwork cells, causing cell stress and eventually apoptosis. After apoptosis occurs, the trabecular meshwork is compromised, leading to an increase in intraocular pressure, a symptom of glaucoma. In this thesis, I have expressed and purified the wild-type olfactomedin (OLF) domain and 24 reported disease-causing variants. I developed a facile thermal stability assay using differential scanning fluorimetry, which follows the unfolding of a protein through the fluorescence of a dye sensitive to hydrophobic regions of a protein. Also in this thesis I have determined melting temperatures for the wild-type and for each of the disease-causing mutants. I have tested the stability of the mutants in the presence of seven osmolytes, with sarcosine and trimethylamine-N-oxide restoring the melting temperature closest to wild-type. Additionally, I expressed and purified three reported single nucleotide polymorphisms (SNPs) (E352Q, E396D, K398R), which are considered benign variants. Variants were also compared by circular dichroism, revealing high b-sheet content and wild-type structure. When compared to previous studies, there is a positive correlation between the melting temperature, and previously reported qualitative assays, which measure the mutant myocilin solubility in detergent, secretion from mammalian cells, and aggregation propensity. Taken together, these data give insight into the relationship between glaucoma genotypes and phenotypes.

This study explored the experience of disability as recounted by school aged, visually impaired adolescents. The primary aim was to explore the manner in which these adolescents thought about, understood and coped with their disability. A second aim explored the extent to which participants’ experiences mirrored those reported in the literature. The design of the study was qualitative with an orientation toward social constructionism. Nine partially sighted and seven blind adolescents comprised the two cohorts of participants who participated in the study. One of the most notable findings supported the argument that disability is a socially constructed phenomenon. Some insights, drawn from psychoanalysis, were also found to be useful. Other findings, a critique of the study, and suggestions for future research are also provided. One of the most important of these involves evaluating the negative and positive consequences of inclusive education.

The premise that mature visual function depends upon the nature of visual experience during development is based primarily on experiments showing that visual deprivation during a 'critical' period early in life causes abnormalities in visual cortex and an enduring loss of spatial vision (amplyopia). There is, however, little evidence that early visual experience atually enables mature vision. Experments in this thesis provide such evidence. The measurement of optomotor responses daily from eye opening permanently enhances optomotor sensitivity and the perception of visual motion. The plasticity allowing this enhancement is transient and peaks in efficacy before the start of the classical 'critical ' period for ocular dominance plasticity. The enhancement is dependent upon optomotor responses generated by the movement of high spatial frequency visual stimuli, and is mediated by the visual cortex. These studies show that a form of experience-dependent plasticity, distinct from that of the critical period, enables mature motion vision. / viii, 107 leaves : ill. (some col.) ; 28 cm.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 7 uppsatser.

Thesis (Ph. D.)--Ohio State University, 2008. / Title from first page of PDF file. Includes bibliographical references (p. 148-156).

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 74-84).

This research focuses on the grief and emotional reactions, especially frustration, of adventitiously visually impaired adults following loss of sight. The traditional grief-following loss theory with the assumption of a time-limited linear grief process, accompanied by diminishing emotions and culminating with acceptance and adjustment has been challenged. Chronic grief assumes a recurrent and continuous grief process, accompanied by increased emotions associated with continual losses related to a chronic loss, such as visual impairment. The question of whether there is a relation between length of time of adventitious visual impairment and the healing affect of time on grief and frustrations has been examined by quantitative and qualitative investigations. The answer to the question of whether time changes and heals everything is not necessarily the case. As always there are more questions than answers, and this research provides further insight into the real world of adventitious visual impairment. / Psychology / M.A. (Psychology)

A Distrofia Muscular de Duchenne (DMD) é uma doença recessiva ligada ao cromossomo X, causada por deleção ou mutação na proteína distrofina, e afeta 1 para cada 3.500 nascidos vivos do sexo masculino. O gene da distrofina é o maior gene do genoma humano e, além das proteínas de tamanho total, ao menos outras 5 isoformas foram identificadas até o momento. A isoforma total da distrofina e outras menores como a Dp260 (transcrita pelo promotor localizado no exon 30; encontrada na camada plexiforme externa da retina) e Dp71 (transcrita pelo promotor localizado no exon 63; encontrada nas células de Muller e membrana limitante interna da retina) são expressas na retina, dentre vários tecidos do corpo. Alterações nos eletrorretinogramas (ERG) de sujeitos com DMD já foram descritas na literatura. Redução da amplitude da onda-b e ERG negativo (razão das.amplitudes entre as ondas b e a menor que 1) são os achados mais comuns principalmente em sujeitos com deleção posterior ao exon 30. Embora estas alterações sejam conhecidas, poucos estudos avaliaram funcionalmente a visão destes sujeitos e, estes concluíram que os sujeitos com DMD apresentam visão de cores, acuidade visual e motilidade ocular normais. Como estas conclusões não refletem os achados eletrofisiológicos, o presente trabalho teve por objetivo aprofundar a avaliação de funções visuais em sujeitos com DMD, utilizando testes psicofisicos mais precisos e sensíveis que os métodos anteriormente empregados. Aplicamos uma bateria de testes que avaliou: a visão de cores (Cambridge Colour Test, Anomaloscópio de Neitz tipo I, lshihara e AO H-R-R) e a sensibilidade ao contraste de luminância (espacial e temporal), em 54 meninos (idade média =14,2 ± 4,1) com DMD, bem como o ERG em um subgrupo de 11 sujeitos. De acordo com a região da deleção no gene foram constituídos 3 grupos: grupo 1 (n=20) - sem deleção, grupo 2 (n=7) - com deleção anterior ao exon 30, grupo 3 (n=27) com deleção posterior ao exon 30. O grupo controle foi composto por 35 meninos com idade equiparada (médias = 15,4 ± 3,9). Os resultados mostraram que 52% dos sujeitos do grupo 3 apresentam defeitos de visão de cores. Surpreendentemente, a maioria destes sujeitos apresentou um defeito no eixo protan-deutan. Os três grupos apresentaram redução na sensibilidade ao contraste espacial e ao contraste temporal para todas as freqüências espaciais e temporais testadas. Houve uma tendência do grupo 3 de ter os piores resultados de contraste espacial. Para os resultados de contraste temporal, diferiram estatisticamente do grupo controle apenas os sujeitos do grupo 3 que tinham defeito de visão de cores. Os parâmetros do ERG de campo total replicaram os dados da literatura mostrando uma diminuição da amplitude e um aumento da latência da onda-b, além de uma razão b/a menor que l. A análise individual dos potenciais oscilatórios mostrou redução significante no 3° e no 4° potenciais, indicando que tanto a via dos cones quanto a dos bastonetes estão afetadas nos sujeitos com.DMD e deleção posterior ao exon 30. A constatação das maiores alterações de função visual nos sujeitos com deleção posterior ao exon 30 leva a sugerir que a distrofina Dp260 tem papel importante na fisiologia retiniana. Em conclusão, o presente trabalho demonstrou que a DMD é acompanhada por perdas visuais em várias funções e que estas perdas podem ser causadas principalmente por modificações na isoforma Dp260 da distrofina / Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder, caused by deletion or mutation in the protein dystrophyn, which affects 1:3500 live male births. The dystrophyn gene is the largest gene in the human genome. The full-length dystrophyn and at least other 5 isoforms have been identified. They are expressed in several tissues of the body including the retina, where the shorter isoforms Dp260 (transcribed by a promoter at the exon 30; founded in the outer plexiform layer of the retina) and Dp71 (transcribed by a promoter at the exon 63; founded in the Muller cells and inner limiting membrane of the retina) have been shown. Alterations in the electroretinograms (ERG) of these subjects have been described in the literature. 13-wave amplitude reduction and -a negative ERG (b/a wave amplitude ratio < 1) are the most common alterations found in subjects with gene deletion downstream exon 30, transcribes Dp260 isoform. Although these alterations are known, the only study that performed 1 evaluations of visual functions in these subjects concluded that they showed normal color vision, visual acuity and ocular motility results. Since these conclusions do not reflect the electrophysiological findings the objective of the present study was to further evaluate the visual function of DMD subjects using more sensitive and precise psychophysical tests than the methods used before. A battery of visual tests was used to evaluate color vision (Cambridge Colour Test, Neitz-1 Anomaloscope, Ishihara and AO H-R-R), luminance contrast sensitivity (spatial and temporal) in 54 boys (mean age = 14,2 ± 4,1) with DMD, and the ERG was also measured in a subgroup (n = 11) of these boys. According with the region of gene deletion, the subjects were divided in 3 groups: group 1 (n = 20) - without gene deletion, group 2 (n = 7) - with gene deletion upstream exon 30, group 3 (n = 27) - with gene deletion downstream exon 30. The control group was composed of 35 age-matched boys (mean-- 15,4 ± 3,9). Our results showed that 52% of the group 3 subjects had color vision defects. Surprisingly, almost all of these boys had a defect in the proten-deutan axis. In all three groups, spatial and temporal contrast sensitivities were lower than those of controls, for all spatial and temporal frequencies tested. Group 3 subjects had a tendency not statistically significant to present the worst results of spatial contrast sensitivities. Temporal contrast sensitivities were significantly different from controls' only for group 3 subjects with color vision defects. The full-field ERG results showed a b-wave amplitude reduction, a longer implicit time and a b/a ratio less than 1. Oscillatory potentials were significantly lower in the 3° and 4° potentials suggesting that that both cone and rod pathways were affected in the DMD subjects with deletion downstream exon 30. To our knowledge there are no descriptions of visual function defects in DMD subjects. The finding that the largest alterationslosses of visual function oceur in the subjects with deletion downstream exon 30 leads us to suggest that the dystrophyn Dp260 has an important role in the physiology of the retina physiology. In conclusion, the present study showed that DMD is accompanied losses in several visual functions and that these losses may be caused mainly by impairment in the Dp260 dystrophyn isoform

Orientador: Fausto Orsi Medola / Banca: Sergio Tosi Rodrigues / Banca: Milton José Cinelli / Resumo: A ausência da visão altera o padrão da marcha e a velocidade de caminhada, aumentando a dependência social e as chances de quedas e acidentes, comprometendo assim a mobilidade independente e a participação social. Dessa forma, é necessário o uso de dispositivos de Tecnologia Assistiva (TA), dentre os quais destaca-se a bengala: um bastão manual com ponteira que auxilia o usuário na orientação da trajetória e detecção de obstáculos. Embora a bengala contribua para a segurança e independência na mobilidade, nota-se ainda resistência na sua utilização, que pode ser explicada pela sua limitação no alcance de obstáculos, podendo ocasionar acidentes e riscos à saúde dos usuários. A bengala eletrônica surge como uma solução para este problema. Através do sensor ultrassom, ela detecta obstáculos acima da linha da cintura emitindo sinais sonoros e táteis. Para avaliar se a nova tecnologia é de fato mais eficiente para mobilidade dos usuários, este projeto de pesquisa propôs a comparação da eficiência de dois tipos de bengala - a tradicional e a eletrônica - através da execução de um trajeto com obstáculos artificiais, analisando o desempenho através das variáveis velocidade de caminhada e porcentagem de detecção de obstáculos. O estudo foi dividido em dois grupos amostrais: participantes vendados sem deficiência visual (N = 31) e participantes com deficiência visual (N = 10). O estudo também avaliou a usabilidade dos dispositivos segundo a perspectiva dos participantes, a satisfação d... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The absence of vision changes the gait pattern and the walking speed, increasing social dependence and the chances of falls and accidents, thus compromising the independent mobility and social participation. Therefore, the use of Assistive Technology (AT) devices is necessary, among which stands out the white cane: a hand stick with a tip that helps the user in the path orientation and obstacles detection. Although the white cane contributes for safety and independence in the mobility, it is noted the resistance in its use, which can be explained by its limitation in the range of obstacles, which may cause accidents and risks to the user's health. The electronic cane arises as a solution to this problem. By the means of an ultrasonic sensor, it detects obstacles above the waistline sending sound and tactile feedback. To evaluate if the new technology is indeed more efficient for the users' mobility, this research project proposed the comparison of efficiency between two types of canes - the traditional white cane and the electronic cane - by the means of a performance of a path with artificial obstacles, analyzing the performance through the variables walking speed and obstacles detection percentage. The study was split into two sample groups: blindfolded participants without visual impairment (N = 31) and participants with visual impairments (N = 10). The study also evaluated the usability of the devices according to the participants' perspective, the AT users' satisfaction ... (Complete abstract click electronic access below) / Mestre

No / PURPOSE. Previous studies suggest that optimal reading speed is unaffected by cataract, yet is significantly reduced in age-related macular degeneration (ARMD ). This raises the question of whether a reading speed test could be developed to assess potential vision after cataract surgery. METHODS. Nineteen subjects with cataract, 15 with ARMD, and 13 control subjects with normal, healthy eyes read Bailey-Lovie word charts aloud, and subsequently, critical print size and optimal reading speed were calculated. Measurements were also taken with the charts in reversed-contrast polarity and after pupillary dilation. RESULTS. Although the subjects with cataract had reduced word acuity and increased critical print size, optimal reading speed was similar to that of the control group at a mean of approximately 100 wpm. Optimal reading speed in the subjects with ARMD was substantially worse (mean of 39 wpm). Reversing the contrast polarity of the charts slightly increased the word acuity and optimal reading speed of the subjects with cataract. CONCLUSIONS. The results suggest that optimal reading speed would be useful as a potential-vision test. The proposed test would use text size of at least 1.32 degrees (1.2 log minimum angle of resolution [logMAR]), and pupil dilation would be unnecessary. A reading test with black letters on a white background would be adequate, because charts with reversed-contrast polarity made minimal difference in reading speed.