Dissertations / Theses on the topic 'Lens of the Eye'
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Bateman, Orval. "The characterisation of eye lens crystallins." Thesis, Birkbeck (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301285.
Full textKeenan, Jonathan. "Crystallin distribution patterns in the eye lens." Thesis, University of Ulster, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.554261.
Full textHott, John Lester. "Photochemical alterations of ocular lens proteins." Diss., Georgia Institute of Technology, 1991. http://hdl.handle.net/1853/30087.
Full textTomlinson, Julie. "Calcium in relation to lens physiology and pathology." Thesis, University of East Anglia, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292537.
Full textChen, Wen-Lung. "Raman spectroscopic/imaging studies of eye lenses and lens proteins." Diss., Georgia Institute of Technology, 1991. http://hdl.handle.net/1853/30431.
Full textWilson, Cynthia Nicole. "A Fully Customizable Anatomically Correct Model of the Crystalline Lens." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20130.
Full textMacDonald, James Tomomi. "The unfolding and stability of eye lens crystallins." Thesis, Birkbeck (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427680.
Full textChandler, Heather Lynn. "Epithelial-mesenchymal transition in the anterior segment of the eye." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1154533588.
Full textWalker, Heather Mhairi. "Investigating the role of the lens in the growth and development of the vertebrate eye." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=225773.
Full textSparrow, John Martin. "The lens in diabetes." Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238162.
Full textLin, Valentine, and Hamad Tarek Sayed. "3D Printing a Maxwell Fish Eye Lens With Periodic Structures." Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-254262.
Full textNichols, Jason Jay. "Evaporative tear film and contact lens factors associated with dry eye symptoms in contact lens wearers." The Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1085771728.
Full textBanks, Eric A. "Connexin 45.6 in lens development : a dissertation /." San Antonio : UTHSC, 2007. http://proquest.umi.com/pqdweb?did=1400957401&sid=1&Fmt=2&clientId=70986&RQT=309&VName=PQD.
Full textNichols, Jason J. "Evaporative tear film and contact lens factors associated with dry eye symptoms in contact lens wearers." Connect to this title online, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1085771728.
Full textTitle from first page of PDF file. Document formatted into pages; contains xiii, 122 p.; also includes graphics Includes bibliographical references (p. 80-94). Available online via OhioLINK's ETD Center
Slight, S. H. "Biochemical studies on the mammalian lens." Thesis, University of Salford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381703.
Full textSousounis, Konstantinos. "Gene Expression During Newt Lens Regeneration and Cephalopod Eye Evolution." University of Dayton / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1405702826.
Full textPrincipi, Sara. "Development of methodologies for estimating the dose to the eye lens in interventional radiology : operational implications of the eye lens new dose limit." Doctoral thesis, Universitat Politècnica de Catalunya, 2017. http://hdl.handle.net/10803/620729.
Full textEvidencias epidemiológicas sobre la manifestación precoz de cataratas u opacidades han comportado la revisión del límite anual de dosis equivalente al cristalino (150 mSv /año) para los trabajadores expuestos a la radiación ionizante. ICRP 118 recomienda reducir dicho límite a 20 mSv por año, promediado en un período de 5 años. Este cambio drástico en el límite de dosis se ha incorporado en las Normas básicas de protección radiológica europeas (Comisión Europea, 2014) e internacionales (IAEA, 2013) y deberán ser transpuestas a la legislación nacional de los Estados miembros en 2018. Actualmente, no se lleva a cabo el control dosimétrico de la dosis al cristalino y no se dispone de recomendaciones internacionales consensuadas sobre cómo llevar a cabo dicho control. Esta tesis presenta diversas propuestas para cubrir las nuevas necesidades metrológicas, dosimétricas y de protección radiológica en el ámbito de la cardiología y radiología intervencionista, asociadas al nuevo cambio legislativo. Se ha desarrollado y puesto a punto un procedimiento para la calibración de dosímetros personales de cristalino en unidades de Hp(3). También se ha caracterizado el dosímetro de cristalino UPC-ELD de acuerdo con la norma IEC 32687 (2012) para campos de radiación fotónica. Dicho dosímetro se ha utilizado en una campaña de medidas en maniquí antropomórfico para la validación de diversos sistemas dosimétricos y para analizar la influencia de la posición del dosímetro para la estimación de la medida de la dosis equivalente en cristalino. Se concluye que la posición óptima del dosímetro de cristalino, es sobre la oreja, en el lado correspondiente al ojo más expuesto, habitualmente el izquierdo. Se efectuaron mediciones en cuatro hospitales españoles utilizando el dosímetro UPC-ELD. Participaron 24 facultativos y 12 enfermeras. Los resultados muestran que aproximadamente el 40% de los médicos y el 25% de las enfermeras superarían el nuevo límite. Paralelamente se ha investigado la relación entre Hp (3) y otras magnitudes como Hp (0,07) determinado con un dosímetro de cuerpo entero situado a nivel de tórax encima del delantal plomado o el KAP registrado en la consola de rayos X. Los resultados ponen de manifiesto que la relación entre Hp (3) y Hp (10) o Hp (0:07), medidas en el tórax, es más reproducible que la relación entre Hp (3) y KAP, en particular en el caso de las enfermeras. La determinación indirecta de la dosis en cristalino presenta importantes incertidumbres puesto que la relación entre las distintas magnitudes depende del tipo de procedimiento, de la posición de la persona y del uso de los sistemas de protección. Por ello, esta metodología sólo se recomienda para la vigilancia individual, si es muy poco probable que la dosis equivalente anual en el cristalino supere 6 mSv, o bien si el objetivo consiste en identificar los puestos de trabajo que pueden requerir un control dosimétrico sistemático. El factor de corrección recomendado para estimar Hp (3) es: Hp (3)= 0.8Hp (0.07) tórax. Cuando no es improbable superar 6 mSv, se recomienda el uso de un dosimetro específico para el cristalino. Mediante simulaciones Monte Carlo se analiza la influencia de varios parámetros en la dosis equivalente en cristalino y se determina la atenuación de distintos tipos de gafas protectoras. En base a los resultados de las simulaciones se propone situar los monitores alejados del haz de rayos X y girar la cabeza de 30º a 45º en dirección opuesta al tubo de RX, dicha posición reduce la dosis en cristalino aproximadamente el 50%, en particular a distancias de 20 cm y 40 cm de la fuente de rayos X. Además, se ha determinado un factor de corrección igual a 0,3 para las gafas de plomo de estilo envolvente y un valor más conservador de 0,5 para otros diseños menos ajustados. Por último, esta tesis subraya la necesidad de mejorar la formación sobre el correcto uso de los sistemas
Li, Dongyun. "The effect of UV-laser radiation on lenses and lens proteins." Thesis, Georgia Institute of Technology, 1989. http://hdl.handle.net/1853/27271.
Full textMcClure, Kate Alexandra. "Tear Film Dynamics Associated with Contact Lens Wear." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1523579680091666.
Full textBergbauer, Katrina L. "Laser raman spectroscopic studies of ocular lens aging and cataractogenesis." Diss., Georgia Institute of Technology, 1991. http://hdl.handle.net/1853/30031.
Full textPoey, S. M. "Infrared thermography of the anterior eye during contact lens wear." Thesis, University of Manchester, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494480.
Full textEvans, Paul James. "Circular dichroism spectroscopy studies of the eye lens crystallin proteins." Thesis, Birkbeck (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437767.
Full textMaksimovic, Srdjan. "Unusual eye design: The compound-lens eyes of Strepsiptera and the scanning eyes of Sunburst Diving Beetle larvae." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1285687000.
Full textWei, Kang. "Bio-inspired Reconfigurable Elastomer-liquid Lens: Design, Actuation and Optimization." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429657034.
Full textSrikanthan, Durga. "Structural studies of small heat shock proteins and eye lens crystallins." Thesis, Birkbeck (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414501.
Full textNajmudin, Shabir. "A structural analysis of eye lens proteins : refinement of yB crystallin." Thesis, Birkbeck (University of London), 1993. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740998.
Full textHook, Darren W. A. "Protection of enzymes by the molecular chaperone #alpha#-Crystalline." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300133.
Full textMiranda, Marco A. L. A. E. "Structural and Optical Changes in the Eye with Soft Contact Lens Wear." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.532229.
Full textHennelly, Michelle Louise. "The light scattering characteristics of the normal and contact lens-wearing eye." Thesis, City University London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367322.
Full textKivlan, Anna Karrer. "An eye for vulgarity : how MoMA saw color through Wild Bill's lens." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39314.
Full textIncludes bibliographical references (p. 67-71).
This thesis is an examination of the 1976 Museum of Modern Art exhibition of color photographs by William Eggleston-the second one-man show of color photography in the museum's history- with particular attention to the exhibition monograph, William Eggleston's Guide. From hundreds of slides, MoMA Director of Photography John Szarkowski dominated the process of selecting the 75 images for the exhibition and 48 to be carefully packaged in the Guide, a faux family photo album/road trip guidebook. It is my contention that, despite their verbal emphasis on the Modernist and universal (rather than Southern) nature of the images, the photographs can be read as being replete with the mythology of the Old South- its decay, vulgarity, and even horror. Through this act of manipulation, the images in the Guide appealed in a voyeuristic way to an elite Northern art world audience, ever eager to reinforce its own intellectual, economic, and ethical superiority over other parts of the country. Due to its presumed "vulgarity" and absence of aesthetic mystique at the time, color photography required for its inaugural moment at the museum a sharp distancing from the documentary tradition and advertising-the complete erasure of social context afforded by a Modernist aesthetic.
(cont.) The two-faced posture maintained by the curator and photographer combined a canny understanding of the cultural power of the images with an overtly Modernist disavowal of it.
by Anna Karrer Kivlan.
S.M.
Best, Nigel. "The predictive ability of clinical tests for contact lens induced dry eye." Thesis, Aston University, 2013. http://publications.aston.ac.uk/19599/.
Full textBarron, Brent Christian. "Characterization of normal aging and cataractous processes in the eye lens by laser raman spectroscopy." Diss., Georgia Institute of Technology, 1988. http://hdl.handle.net/1853/30052.
Full textDerham, Barry K. "The effects of ageing on #alpha#-crystallin, a molecular chaperone." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325297.
Full textMizdrak, Jasminka. "Human lens chemistry: UV filters and age-related nuclear cataract." Australia : Macquarie University, 2007. http://hdl.handle.net/1959.14/16855.
Full textThesis (PhD) -- Macquarie University, Division of Environmental and Life Sciences, Dept. of Chemistry and Biomolecular Sciences, 2007.
Bibliography: p. 243-277.
Introduction -- A convenient synthesis of 30HKG -- Facile synthesis of the UV filter compounds 30HKyn and AHBG -- Synthesis, identification and quantification of novel human lens metabolites -- Modification of bovine lens protein with UV filters and related metabolites -- Effect of UV light on UV filter-treated lens proteins -- Conclusions and future directions.
The kynurenine-based UV filters are unstable under physiological conditions and undergo side chain deamination, resulting in α,β-unsaturated carbonyl compounds. These compounds can react with free or protein bound nucleophiles in the lens via Michael addition. The key sites of the UV filters kynurenine (Kyn) and 3-hydroxykynurenine (3OHKyn) modification in human lenses include cysteine (Cys), and to a lesser extent, lysine (Lys) and histidine (His) residues. Recent in vivo studies have revealed that 3-hydroxykynurenine-O-β-D-glucoside (3OHKG) binds to Cys residues of lens crystallins in older normal human lenses. As a result of this binding, human lens proteins become progressively modified by UV filters in an age-dependent manner, contributing to changes that occur with the development of age-related nuclear (ARN) cataract. Upon exposure to UV light, free UV filters are poor photosensitisers, however the role of protein-bound species is less clear. It has been recently demonstrated that Kyn, when bound to lens proteins, becomes more susceptible to photo-oxidation by UV light. Therefore, the investigation of 3OHKG binding to lens proteins, and the effect of UV light on proteins modified with 3OHKG and 3OHKyn, were major aims of this study. As a result of the role of these compounds as UV filters and their possible involvement in ARN cataract formation, it is crucial to understand the nature, concentration and modes of action of the UV filters and their metabolites present in the human lenses. Therefore, an additional aim was to investigate human lenses for the presence of novel kynurenine-based human lens metabolites and examine their reactivity.--As 3OHKG is not commercially available, to conduct protein binding studies, an initial aim of this study was to synthesise 3OHKG (Chapter 2). Through the expansion and optimisation of a literature procedure, 3OHKG was successfully synthesised using commercially available and inexpensive reagents, and applying green chemistry principles, where toxic and corrosive reagents were replaced with benign reagents and solvent-free and microwave chemistry was used. A detailed investigation of different reaction conditions was also conducted, resulting in either the improvement of reaction yields or reaction time compared to the literature method. Applying the same synthetic strategy, and using key precursors from the synthesis of 3OHKG, the UV filters 3OHKyn and 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid-O-β-D-glucoside (AHBG), were also successfully synthesised (Chapter 3).
Chapter 4 describes the investigation of both normal and cataractous human lenses in an attempt to identify novel human lens metabolites derived from deaminated Kyn and 3OHKyn (Chapter 4, Part A). Initially, 4-(2-aminophenyl)-4-oxobutanoic acid (AHA), glutathionyl-kynurenine (GSH-Kyn), kynurenine yellow (Kyn yellow), 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid (AHB), glutathionyl-3-hydroxykynurenine (GSH-3OHKyn) and 3-hydroxykynurenine yellow (3OHKyn yellow) were synthesised and human lenses were examined for their presence. AHA and AHB were synthesised from similar precursors to those used in the synthesis of 3OHKG, while the GSH adducts and yellow compounds were synthesised from Kyn and 3OHKyn via base induced deamination. Following isolation and structural elucidation, AHA, AHB and GSH-Kyn were confirmed as novel human lens metabolites. They were quantified in low pmol/mg lens (dry mass) levels in normal and cataractous lenses of all ages, while GSH-3OHKyn, Kyn yellow and 3OHKyn yellow were not detected. In contrast to AHA, the lens metabolites AHB, GSH-Kyn and GSH-3OHKyn were found to be unstable at physiological pH. The spectral properties of these compounds suggest that they may act as UV filters. --Chapter 4 (Part B) also describes the identification and characterisation of a novel human lens UV filter, cysteinyl-3-hydroxykynurenine -O-β-D-glucoside (Cys-3OHKG). An authentic standard was synthesised via Michael addition of cysteine to deaminated 3OHKG. Cys-3OHKG was detected in low pmol/mg lens (dry mass) levels in normal lenses only after the 5th decade of life and was absent in cataractous lenses. Cys-3OHKG showed rapid decomposition at physiological pH.
Chapter 5 describes the identification and quantification of amino acids involved in covalent binding of 3OHKG to lens proteins. Model studies with bovine lens proteins and 3OHKG at pH 7.2 and 9.5 were undertaken. The amino acid adducts were identified via total synthesis and spectral analysis, and subsequently quantified upon acid hydrolysis of the modified lens proteins. Under both pH conditions, 3OHKG was found to react with lens proteins predominantly via Cys residues with low levels of binding also detected at Lys residues. Comparative studies with Kyn (pH 9.5) and 3OHKyn (pH 7.2 and 9.5) resulted in modified lens proteins at Cys residues, with only minor modification at Lys residues at pH 9.5. The extent of modification was found to be significantly higher at pH 9.5 in all cases. His adducts were not identified. 3OHKG-, Kyn- and 3OHKyn-modified lens proteins were found to be coloured and fluorescent, resembling those of aged and ARN cataractous lenses. In contrast, AHB and AHA, which can not form α,β-unsaturated carbonyl compounds, resulted in non-covalent modification of lens proteins. AHB may contribute to lens colouration and fluorescence as further reactions of this material yielded species that have similar characteristics to those identified from 3OHKyn modification. These species are postulated to arise via auto-oxidation of the o-aminophenol moiety present in both 3OHKyn and AHB.--In Chapter 6, the potential roles of 3OHKG and 3OHKyn, and the related species AHA and AHB, in generating reactive oxygen species and protein damage following illumination with UV light was examined. The UV filter compounds were examined in both their free and protein-bound forms. Kyn-modified proteins were used as a positive control. Exposure of these compounds to UV light (λ 305-385 nm) has been shown to generate H2O2 and protein-bound peroxides in a time-dependent manner, with shorter wavelengths generating more peroxides. The yields of peroxides were observed to be highly dependent on the nature of the UV filter compound and whether these species were free or protein bound, with much higher levels being detected with the bound species. Thus, protein-bound 3OHKyn yielded higher levels of peroxide than 3OHKG, with these levels, in turn, higher than for the free UV filter compounds. AHB-treated lens proteins resulted in formation of low but statistically significant levels of peroxides, while AHA-treated lens proteins resulted in insignificant peroxide formation. The consequences of these photochemical reactions have been examined by quantifying protein-bound tyrosine oxidation products (3,4-dihydroxyphenylalanine [DOPA], di-tyrosine [di-Tyr]) and protein cross-linking. 3OHKG-modified proteins gave elevated levels of di-Tyr, but not DOPA, whereas 3OHKyn-modified protein gave the inverse. DOPA formation was observed to be independent of illumination and most likely arose via o-aminophenol auto-oxidation. AHB- and AHA-treated lens proteins resulted in statistically insignificant di-Tyr formation, while a light independent increase in DOPA was observed for both samples. Both reducible (disulfide) and non-reducible cross-links were detected in modified proteins following illumination. These linkages were present at lower levels in modified, but non-illuminated proteins, and absent from unmodified protein samples.
This work has provided an optimised synthetic procedure for 3OHKG and other lens metabolites (Chapters 2 and 3). Four novel lens metabolites have been identified and quantified in normal and cataractous human lenses (Chapter 4). Subsequent experiments, described in Chapter 5, identified the major covalent binding sites of 3OHKG to lens proteins, while AHA and AHB showed non-covalent binding. Further work described in Chapter 6 showed that protein-bound 3OHKG, Kyn and 3OHKyn were better photosensitisers of oxidative damage than in their unbound state. Together, this research has provided strong evidence that post-translational modifications of lens proteins by kynurenine-based metabolites and their interaction with UV light appear, at least in part, responsible for the age-dependent colouration of human lenses and an elevated level of oxidative stress in older lenses. These processes may contribute to the progression of ARN cataract.
Mode of access: World Wide Web.
xxxix, 308 p. ill. (some col.)
Pult, Heiko. "The predictive ability of clinical tests for dry eye in contact lens wear." Thesis, Cardiff University, 2008. http://orca.cf.ac.uk/54731/.
Full textSandilands, Aileen. "Characterisation of the intermediate filament proteins filensin and CP49 within the eye lens." Thesis, University of Dundee, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441633.
Full textOppermann, Brian P. "Identification, localization and metal catalyzed induction of specific metallothionein isoforms expressed by the adult human lens." Morgantown, W. Va. : [West Virginia University Libraries], 2001. http://etd.wvu.edu/templates/showETD.cfm?recnum=1846.
Full textTitle from document title page. Document formatted into pages; contains vi, 43 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 37-43).
Hager, Michele LynnManeca. "A Study of Contact Lens Comfort in Patients Wearing Comfilcon A Soft Contact Lenses Compared to Their Habitual Soft Contact Lenses." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1243711014.
Full textSchultz, Kristin E. "Accommodative microfluctuations, crystalline lens tension, ciliary body thickness, and refractive error in children." Columbus, Ohio : Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1240445960.
Full textDube, Zack. "Computational Reconstruction of the Physical Eye Using a New Gradient Index of Refraction Model." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34791.
Full textRueff, Erin. "Contact lens induced dry eye and binocular vision disorders: A study of similar symptoms." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397167126.
Full textRamamoorthy, Padmapriya. "HIGH MOLECULAR WEIGHT TEAR PROTEINS AND OCULAR SURFACE MUCINS IN CONTACT LENS-RELATED DRY EYE." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1316523981.
Full textParker, Nicole Renee. "The role of kynurenine and UV light in lens protein modification." Access electronically, 2005. http://www.library.uow.edu.au/adt-NWU/public/adt-NWU20060720.111305/index.html.
Full textTypescript. EMBARGOED - This thesis is subject to a 12 month embargo (07/03/06 to 07/03/07) and may only be viewed and copied with the permission of the author. For further information please Contact the Archivist. Includes bibliographical references: leaf 236-266.
Arnberg, Philip, and Petersson Oscar Barreira. "Design of a Maxwell Fish-Eye Lens in PCB Technology With a Glide-Symmetric Metasurface." Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-254263.
Full textColom, diego Adai. "From eye lens cells to lens membrane proteins : Development and application of a hybrid high-speed atomic force microscopy/optical microscopy setup." Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4033.
Full textI used the AFM and HS-AFM for characterise the eye lens and the eye lens membrane protein, AQP0 and connexon.A QP0-AQP0 interaction energy is -2.7kBT, it is important for the formation of junctional microdomains, which keep the distance between the cells lens and lens transparency. this is the first report which is present time the visualization of unlabelled membrane proteins on living cells under physiological conditions. AQP1 can not maintain the lens transparency because it does not form junctional microdomains
Yao, Jianchao, and 姚劍超. "Predicting the 3D structure of human aquaporin-0 protein in eye lens using computational tools." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B2948540X.
Full textFlaugh, Shannon L. "Folding, stability and aggregation of the long-lived eye lens protein human gamma D crystallin." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/34572.
Full textVita.
Includes bibliographical references (p. 179-194).
Human [gamma]D crystallin (H[gamma]D-Crys) is a monomeric, two domain, primarily P-sheet protein found in high concentrations in the human eye lens. H[gamma]D-Crys and other crystallins are found in insoluble protein inclusions associated with the eye disease cataract. H[gamma]D-Crys is expressed in utero and does not regenerate during life, thus necessitating high stability and solubility. Covalent damage, including glutamine deamidation, of the lens crystallins increases with age and as a result of exposure to environmental insults. Such covalent damage may cause partial-unfolding into aggregation-prone confomations that cause cataract. The in vitro stability of H[gamma]D-Crys was analyzed in the denaturant guanidine h[gamma]Drochloride at pH 7.0 and 370C. An off-pathway aggregation reaction that competed with refolding was previously reported when H[gamma]D-Crys was refolded to less than 1 M GuHC1. Equilibrium transitions of H[gamma]D-Crys were best fit to a three-state model suggesting the presence of a partially-folded intermediate that likely had a structured C-terminal domain (C-td) and unstructured N-terminal domain (N-td). Similarly, previous analyses revealed a sequential domain refolding pathway where the C-td refolds first followed by the N-td.
(cont.) These findings suggest that the inter-domain interface of H[gamma]D-Crys is important in both folding and stability. The domain interface of H[gamma]D-Crys contains a central h[gamma]Drophobic cluster of six residues and two pairs of peripheral interacting residues. To test this importance of these residues in folding and stability, site-directed alanine mutants were constructed at all ten positions and properties of the mutant proteins were analyzed. Single mutations of h[gamma]Drophobic domain interface residues caused a decrease in stability of the N-td, but did not affect stability of the C-td. Similarly, stability of the N-td but not the C-td was reduced as a result of single and double mutations of peripheral interface residues. Minimal to no interaction energy was observed for the peripheral residues suggesting they contribute to stability indirectly, perhaps by shielding the central h[gamma]Drophobic cluster from solvent. Both the h[gamma]Drophobic and peripheral domain interface alanine mutants also had reduced rates of productive refolding for the N-td while refolding rates for the C-td were unchanged. These results suggest a productive folding pathway where the C-td refolds first and domain interface residues of the structured C-td act as a nucleating center for refolding of the N-td.
(cont.) Effects on N-td refolding rates were most prominent for the h[gamma]Drophobic residues indicating the importance of proper h[gamma]Drophobic burial during refolding. The peripheral domain interface residues of H[gamma]D-Crys include a pair of two glutamines that are targets for covalent damage during aging. Deamidation mimics at these sites were constructed by site directed mutagenesis of glutamine to glutamate. Properties of the mutants were analyzed to assess the affects of deamidation on stability and folding. Similar to the alanine mutants at these sites, the deamidation mutants had a destabilized N-td but not C-td at pH 7.0. In contrast, stabilities of the mutants were indistinguishable from wild type at pH 3.0. The N-td of the deamidation mutants also unfolded faster than that of wild type during kinetic unfolding. These results indicate that deamidation of domain interface glutamines destabilizes H[gamma]D-Crys and lowers the kinetic barrier to unfolding. A reduction in the thermodynamic and kinetic stability as a result of domain interface deamidation could result in the population of partially-unfolded conformations in the lens that may aggregate through mechanisms such as domain swapping or loop-sheet insertion.
by Shannon L. Flaugh.
Ph.D.
Mills-Henry, Ishara Amenti Rakem. "Stability, unfolding, and aggregation of the gamma D and gamma S human eye lens crystallins." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/38627.
Full textIncludes bibliographical references (v. 2, leaves 189-208).
The transparency of the human eye lens depends on the properties of the a- crystallin and py-crystallin families of proteins, which accumulate to very high concentrations in mature lens fiber cells. The 0- and y-crystallins are thought to be primarily structural proteins while a-crystallin possess an additional chaperone activity. Aggregation of partially unfolded or covalently damaged forms of these proteins results in cataract, which is the leading cause of blindness in the world. The biochemical basis of the very high crystallin stability, and the nature of the misfolded, modified, or aggregated states, are thus of considerable importance in understanding the etiology of loss of lens transparency. All vertebrate P- and y-crystallins are homologous and contain two highly symmetrical domains with a hydrophobic interface connected by an interdomain linker. The overall sequences, fold topology, and domain interfaces of vertebrate py-crystallins are highly conserved. The two domain 0- and y-crystallins are believed to have evolved by gene duplication and fusion from an ancestral single domain py-crystallin. This thesis is focused on stability and aggregation properties of human yD crystallin (yDwT) and human yS crystallin (ySwT), two of the most abundant proteins in the human lens.
(cont.) Terminally differentiated fiber cells in the central nucleus of the lens are enucleated and devoid of organelles. The yD crystallins synthesized in utero must remain stable and soluble throughout life. The yS protein is more prevalent in the cortical regions of the lens, where protein degradation and synthesis do occur. Given the importance of long-term solubility for the crystallins, it seems likely that selection for the two-domain form is related to the need for very long-term stability. Comparison of the stabilities of the isolated domains and the intact protein indicated that the domain interface contributes a AGH20 of~ 4.2 kcal*mol-l to the stability of the complete yDwT two-domain protein. The differential stability observed for the yD isolated domains was not as distinct for the yS isolated domains. These results support the idea that selection for increased thermal stability was one of the factors leading to the evolution of two domain crystallins. A distinct hysteresis occurs during equilibrium unfolding and refolding, due to a kinetic barrier in the unfolding pathway. By extrapolating kinetic unfolding results from denaturing GuHCl concentrations to buffer, I show that the ti2 for the initial unfolding step is -19 years. The value extrapolated for the YSwT is not as long, though still significant. This supports the earlier conclusion that the domain interface is an important source of stability.
(cont.) Previous studies had shown that upon dilution from denaturant partially folded intermediates of yD crystallin formed highly ordered fibrous aggregates that were not amyloid in nature. This aggregation reaction of yDwT polypeptide chains competing with productive refolding provided a model for cataractogenesis in vitro. The structurally homologous ySwT crystallin did not exhibit an off-pathway aggregation under the same conditions as yDwT. This suggested that the pathway of aggregation involved specific amino acids or sequences essential for association and was not a general feature of the y- crystallins. To investigate this disparity between two structurally similar crystallins, chimera proteins were created in an attempt to narrow down regions of the protein that promoted aggregation in DwTr or regions in ySwT that inhibited aggregation. The aggregation behavior upon refolding was analyzed for the chimeras and isolated single domains. Partitioning of refolding chains into the aggregation pathway was strongest for the full-length proteins that retained the yD interface. This result is consistent with a domain swapping mechanism for the off-pathway aggregation of the crystallins. This aggregation reaction may be coupled to the increased stability of the yD-protein, as a kind of evolutionary cost of the extremely stable and long-lived native state conformation.
by Ishara Amenti Rakem Mills-Henry.
Ph.D.
Bailey, Sheldon T. "Transparent Tissues and Porous Thin Films: A Brillouin Light Scattering Study." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1357248652.
Full textDay, Kevin Douglas. "The mechanics of a hydrogel contact lens on the human eye with a lubricating tear layer." Thesis, Massachusetts Institute of Technology, 1997. http://hdl.handle.net/1721.1/43596.
Full textIncludes bibliographical references (p. 113-114).
The mechanics governing the fit of a soft contact lens on the eye are examined through the development of a finite element analysis model. A linearly elastic lens is placed on a rigid eye with a lubricating viscoelastic tear layer. The mechanics of fit are described in terms of the pressure distribution through the tear layer, the contact pressure at the lens/tear interface, the tear film thickness, and the bending and membrane stresses in the contact lens itself. A parametric study is performed to investigate the impact of model assumptions of initial tear film thickness, tear film material properties, and eye geometries on the results predicted by the numerical simulations. Further study is performed to investigate the impact of certain geometric lens parameters and how variations in lens thickness, sagittal height, bevel curve design, and back surface design affect the mechanics of the contact lens. A three dimensional model is also developed to investigate mobility and stability issues. The strain energy is monitored as the lens is moved across the eye as it would move during a blink of the eye. Mobility is measured both through the total strain energy present in the lens and the strain energy gradient near the equilibrium position of the lens as a function of displacement on the eye. In addition to strain energy values, the force required to move the lens across the surface of the eye is monitored. The long term goal of this work is to develop a numerical tool to assist in the design and development of new lens geometries for better fit and mobility of soft contact lenses.
by Kevin Douglas Day.
S.M.