Thesis (Ph. D.)--University of Chicago. / "Reprinted from the Journal of comparartive neurology and psychology, vol. XVI, no. 4, 1906." Includes bibliographical references (p. 28-31). Also available on the Internet.

Thesis (Ph. D.)--Virginia Commonwealth University, 2006. / Prepared for: Dept. of Anatomy and Neurobiology. Bibliography: leaves 159-181. Also available online.

Peripherin, a membrane protein with an apparent molecular weight of 34 kDa, has been previously localized to the rim region of the vertebrate rod photoreceptor disk membrane using monoclonal antibodies and immunocytochemical labelling techniques. As an initial step in determining the structure and function of this protein, cDNA containing its coding sequence has been cloned and sequenced. A bovine retinal ʎgtll expression library was screened with antiperipherin monoclonal antibodies, and a 583 base pair clone was initially isolated. The remaining part of the coding sequence was obtained from subsequent rescreenings of the same library and an independent ʎgt10 library. A C-terminal CNBr fragment of peripherin was purified by immunoaffinity chromatography and reverse phase high-performance liquid chromatography. The amino acid sequence of the isolated C-terminal peptide and the N-terminal sequence analysis of immunoaffinity purified peripherin are in agreement with the cDNA sequence. At the amino acid level, the sequence of peripherin has 92.5% sequence identity to the gene proposed to be responsible for the retinal degeneration slow defect in mice (Travis et al.(1989) Nature 338, 70-73) The differences between the two sequences can be attributed to species differences. The identity of the retinal degeneration slow gene product and its intracellular localization were previously unknown. The cDNA sequence of peripherin predicts that there are possibly four transmembrane domains. On the basis of immunocytochemical studies and sequence analysis, the hydrophilic C-terminal segment containing the antigenic sites for the antiperipherin monoclonal antibodies has been localized on the cytoplasmic side of the disk membrane. There are three consensus sequences for asparagine linked glycosylation. Deglycosylation studies have indicated that at least one of these sites is utilized. The complete coding sequence of peripherin was expressed in COS-1 cells. Western blot analysis of the expressed peripherin suggest that it exists as a homodimer in the absence of a reducing agent. The possible function of peripherin in relation to its primary structure is discussed. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Retinitis pigmentosa (RP) is a collection of inherited retinal degenerations that afflicts 50,000- 100,000 people in the United States. The hallmark pathology of RP is apoptosis of photoreceptor cells. Currently there is no treatment for this disease. The equivalent light hypothesis states that some RP mutations cause retinal degeneration by mimicking a continuous phototransduction signal. We tested this hypothesis in transducin knockout (TKO-/-) mice, deficient for the a - subunit of transducin, the heterotrimeric G-protein which mediates light signaling in photoreceptors. Methods: We used light microscopy to compare the retinal morphology of TKO-/- and wild-type (TKO+/+) mice: 1) exposed to continuous bright light, or 2) crossed with mice carrying three different rhodopsin mutations leading to retinal degeneration: A) Proline347Serine (P347S), B) Valine20Giycine, Proline23Histidine, Proline27Leucine (VPP), and C) Lysine296Giutamic acid (K296E). Results: We predicted two types of photoreceptor cell apoptosis: 1) signal-dependent mutants in which degeneration was blocked in the absence of transducin, and 2) signal-independent mutants, not affected by the presence or absence of transducin signaling. To our surprise,we found three classes of retinal degeneration: 1) the VPP triple mutant caused photoreceptor apoptosis, at the same rate, regardless of the presence or absence of a-transducin, 2) the P347S and K296E opsin mutants caused an accelerated rate of degeneration on the TKO -/- background as compared to on the TKO+/+ background, and 3) the damaging effects of continuous light were retarded on the null transducin background. These data support the equivalent light hypothesis as a mechanism for some, but not all forms of retinal degeneration. Thus, the cellular signal that triggers photoreceptor apoptosis can occur either upstream or downstream of transducin signaling. Classifying different types of mutations that lead to photoreceptor cell death will be important for determining effective therapies for different classes of human retinal degeneration. / 2999-01-01

Abstract not available

Neurodegeneration is a collective term for the progressive loss of structure, function or even death of neurons. This includes diseases like Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease and motor neuron disease. Recent researches have shown great interest in the role of tau proteins, which have versatile functions including microtubule stabilization and signal relay in the central nervous system. Retina and optic nerve, being part of the central nervous system, can also be affected by similar processes. In neurodegenerative diseases visual disturbances including difficulties in reading and finding object, depth perception, perceiving structure from motion, color recognition and impairment in spatial contrast sensitivity have all been observed. Some of these defects may be attributed to changes at ocular level. The effect of tau mutation was investigated in this study utilizing a transgenic P301L tau mice model. Morphometric analysis has been utilized to quatify the neurodegenerative changes, including the thickness of inner nuclear layer(INL), density of retinal ganglion cells(RGCs) and size of RGCs. Retinal sections stained by hematoxylin and eosin(H&E) were analyzed. Comparisons were made between the P301L tau mice and the control mice in addition to comparisons between different age groups. The study found that there was a significant decrease of thickness of INL of P301L tau mice when compared with control mice. The effect was more pronounced in the peripheral area and the effect increased with age. Regarding density of RGCs, P301L tau mice showed a similar age-related decline as control mice. And regarding the size of RGCs, the RGCs from P301L tau mice increased in size with age and the RGCs from control mice decreased in size with age. / published_or_final_version / Anatomy / Master / Master of Medical Sciences

Thesis (Ph. D.)--University of Sydney, 2008. / Title from title screen (viewed 18 June 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Department of Clinical Ophthalmology and Eye Health, Faculty of Medicine. Degree awarded 2008; thesis submitted 2007. Includes bibliographical references. Also available in print form.

Neurons establish complex networks within the nervous system allowing for rapid cell-cell communication via their long, thin axonal processes. These wire-thin projections are susceptible to a number of insults or injuries, and axonal damage can lead to disruption in signal propagation and an overall dysfunction of the neural network. Recent research focused on investigating the underlying mechanisms of injury-induced axon degeneration led to the discovery of a number of endogenous, pro-degenerative molecules such as dSarm/Sarm1, Highwire/Phr1, and Axundead. These signaling molecules are thought to execute axon degeneration in response to injury locally within the distal severed axon, but the exact mechanism of action is unclear. To further identify novel participants of the axon death signaling cascade, we performed an unbiased forward genetic mutagenesis screen using the sensory neurons within the adult wing of Drosophila melanogaster. We identified a novel role for the C2H2 zinc finger transcription factor, Pebbled (Peb)/Ras-responsive element binding protein 1 (RREB1) in partially suppressing injury-induced axon degeneration. Loss of function peb mutant glutamatergic neurons present two distinct axon degeneration defects: either complete protection from axotomy, or they exhibit a novel phenotype in which axons fragment into long, continuous pieces instead of undergoing complete degeneration. Additionally, we show an enhancement of the peb protective phenotype when dSarm levels are decreased, but not with reduced levels of axundead. These data provide the first evidence of a transcription factor involved in regulating injury-induced axon degeneration signaling in vivo.

The purpose of this project is to find a mathematical model to describe the vision profile of patients after treatment for choroidal neovascularization. In this model the dependent variable is the level of vision which will be predicted by time after treatment and a number of other variables measured before treatment. A standard multiple regression analysis is used to find significant predictor variables, to investigate interactions and an appropriate transformation. To take the correlation of observations on the same patient into account a linear mixed effects model is fitted. Finally the usefulness of a nonlinear mixed effects model is investigated. / Thesis / Master of Science (MS)

published_or_final_version / abstract / Orthopaedics and Traumatology / Master / Master of Philosophy