Yang, Yaping. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 156-165). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

Visual function degrades with increasing age, in absence of frank disease, and affects both photopic and scotopic sensitivity. The mechanisms underlying these impairments may be related to biological (e.g., neural, optical) and environmental (e.g., smoking, dietary) factors. Recent evidence suggests that visual function may be improved following retinal carotenoid supplementation, both, in healthy and diseased eyes. Retinal carotenoids accumulate within the retina to form the macular pigment (MP) - a biomarker of antioxidant status of the eye and retinal disease risk. The objectives of this thesis were manyfold. First, the extent of vision loss (particularly scotopic sensitivity) in healthy ageing was examined. The results of this investigation showed that dark adaptation recovery slows with increasing age despite no significant change in visual acuity or fundus appearance. The technique described had excellent repeatability and correlated well with previous research. The potential link between MP and dark adaptation was also examined. The results showed that macular pigment optical density (MPOD) was correlated with a specific parameter of dark adaptation (S2) - a sensitive marker of functional degradation in normal ageing and retinal disease. The main part of this thesis sought to investigate the effect of MP augmentation on visual function in a large group of observers aged between 50 and 90 years old. The baseline data from this clinical trial revealed very interesting findings with regards to unhealthy lifestyle behaviours, health status and statin use. Subjects taking statins were identified (n = 25) and matched with 25 participants not using statins for age and body mass index. It was found that statin users had a higher proportion of males, higher prevalence of current smoking status and poorer general health (e.g. hypertension, high cholesterol and heart disease). Statin users also had significantly reduced MPOD, prolonged photostress recovery time, and deficits in a number of dark adaptation parameters. In a separate analysis of the whole group (n= 74, mean age 65.51), smokers were found to have reduced MPOD, slower S2, higher prevalence of high cholesterol and lower fruit and vegetable intake. MPOD was also reduced among obese subjects. The impact of MP augmentation on visual function in normal older subjects was assessed (n = 74, mean age 65.51) in a 12 month, randomized, double-blind, placebo-controlled study. Active formulation consisted of 20 mg lutein combined with vitamins and minerals. Data were collected at baseline, 6 months and 12 months. The results showed that, despite a 24% MPOD increase in the active group, there were no significant differences between the two groups over the three visits for any of the visual parameters. Given the increasing size of the older adult population in developed countries, research aimed at slowing or reversing age-related declines in vision is much needed both from an economical and psycho-social perspective. The results of the studies presented in this thesis show that lifestyle, health status and certain medications can adversely affect visual function in normal ageing. MP augmentation, however, had no effect on visual function. Further research is warranted, particularly paying close attention to subjects engaging in several unhealthy lifestyle/dietary behaviours, statin users and those with low MPOD and suboptimal visual function.

L'àcid retinoic, en les seves formes tot-trans- i 9-cis-, actua com a lligand de receptors nuclears específics, i és essencial en processos de creixement, desenvolupament i manteniment epitelial. La via de formació de l'àcid retinoic inclou dos pasos d'oxidació, de retinol a retinal i de retinal a àcid retinoic. S'han descrit diversos enzims que poden participar en el primer pas, com les ADH i les RDH, però es desconeix la contribució de cada enzim en el procés.S'han clonat, expressat i purificat ADH1B1, ADH2B2 i ADH4 humanes, i també ADH1 i ADH4 de ratolí que, per primera vegada, s'han caracteritzat en la seva forma recombinant. S'han determinat les constants cinètiques de totes aquestes ADHs amb tot-trans- i 7-cis-, 9-cis-, 11-cis- i 13-cis-retinol i els corresponents retinals. En general, les ADH4 humana i de ratolí mostren constants cinètiques similars, i són més eficients que les ADH1. Totes les ADHs utilitzen com a substrats tant 11-cis-retinol com 11-cis-retinal, compostos rellevants en el cicle visual. S'ha observat que l'ADH4 mostra especificitat per a l'oxidació d'11-cis-retinol sobre la reducció d'11-cis-retinal, una propietat única entre totes les ADHs per a qualsevol parella de substrats alcohol/aldehid. Mitjançant mètodes de simulació molecular, i clonatge, expressió i caracterització del mutant de l'ADH4 humana M141L, hem demostrat que el residu 141, situat a la regió mitjana del túnel hidrofòbic del seti actiu de l'ADH, és essencial per definir aquesta especificitat de l'ADH4 sobre les ADH1. La immunolocalització de l'ADH4 a l'epiteli pigmentat i en moltes capes de la retina, dóna suport a la participació de l'ADH4 en diferents reaccions amb retinoides. L'activitat citosòlica de l'ADH4 en l'epiteli pigmentat pot ser complementària a l'activitat 11-cis-retinol deshidrogenasa de la RDH5, necessària per completar el cicle visual, i pot estar també implicada en la generació d'àcid retinoic a les capes neuronals de la retina.Una altra família de retinoides està constituïda per derivats oxidats en l'anell ciclohexè, com per exemple els 4-oxo-, 4-hidroxi- i 3,4-dideshidroretinol i els corresponents retinals. Tot i que són compostos poc estudiats, es coneix que alguns derivats, com els àcids 4-oxo- i el 3,4-dideshidroretinoic poden interaccionar amb receptors nuclears. Les cinètiques dels enzims ADH1B1, ADH2B2 i ADH4 humanes, i també ADH1 i ADH4 de ratolí, indiquen que el 4-oxo-retinal i el 4-hidroxi-retinol són els substrats amb una eficiència catalítica més alta d'entre tots els retinoides, especialment pel que fa a les ADH4, mentre que els 3,4-dideshidroretinoides presenten una activitat similar a la dels tot-trans-retinoides. Les dades obtingudes in vitro recolzen l'existència d'una via metabòlica per a la formació dels àcids retinoics oxidats en l'anell a partir dels corresponents retinols, amb la participació de l'ADH. Finalment, hem comprovat que la presència de Tween 80 provoca una disminució de l'activitat que resulta en una aparent inhibició competitiva en les cinètiques de l'ADH per al tot-trans-retinol, amb un augment de la Km i disminució de l'eficiència catalítica en augmentar la concentració del detergent. Això implica que els valors reals de Km són molt inferiors als publicats fins ara, tradicionalment obtinguts en presència de 0,02 % de Tween 80. Així, les ADHs presenten valors de Km pròxims als de les RDHs i, per tant, la contribució al metabolisme dels retinoides podria ser similar per a ambdós sistemes enzimàtics. Hem comprovat, espectrofotomètricament i per HPLC, que el Tween 80 manté l'estabilitat de la solució aquosa de retinoides, i que permet obtenir resultats reproduïbles i comparables entre diferents ADHs. / Studies in knockout mice support the involvement of alcohol dehydrogenases ADH1 and ADH4 in retinoid metabolism, although kinetics with retinoids are not known for the mouse enzymes. Moreover, a role of ADH in the eye retinoid interconversions cannot be ascertained due to the lack of information on the kinetics with 11-cis-retinoids. We report here the kinetics of human ADH1B1, ADH1B2, ADH4, and mouse ADH1 and ADH4 with all-trans-, 7-cis-, 9-cis-, 11-cis-, and 13-cis-isomers of retinol and retinal. These retinoids are substrates for all enzymes tested, except the 13-cis isomers which are not used by ADH1. In general human and mouse ADH4 exhibit similar activity, higher than that of ADH1, while mouse ADH1 is more efficient than the homologous human enzymes. All tested ADHs use 11-cis-retinoids efficiently. ADH4 shows much higher kcat/Km values for 11-cis-retinol oxidation than for 11-cis-retinal reduction, a unique property among mammalian ADHs for any alcohol/aldehyde substrate pair. Docking simulations and the kinetic properties of the human ADH4 M141L mutant demonstrated that residue 141, in the middle region of the active site, is essential for such ADH4 specificity. The distinct kinetics of ADH4 with 11-cis-retinol, its wide specificity with retinol isomers and its immunolocalization in several retinal cell layers, including pigment epithelium, support a role of this enzyme in the various retinol oxidations that occur in retina. Cytosolic ADH4 activity may complement the isomer-specific microsomal enzymes involved in photopigment regeneration and retinoic acid synthesis.On the other hand, alcohol dehydrogenases (ADH1 and ADH4) actively use retinoids oxidized at the cyclohexenyl ring (4-oxo-, 4-hydroxy- and 3,4-didehydro-retinoids), which are functional compounds in several cells and tissues (i.e. in human skin). Remarkably, activities with 4-oxo-retinal and 4-hydroxy-retinol (kcat = 2050 min-1 for ADH4) are the highest among retinoids, similar to those of the best aliphatic alcohols. Thus, ADH1 and ADH4 provide a metabolic pathway for the synthesis of the corresponding retinoic acids.Finally, Tween 80, a widely used detergent in the retinoid activity assay, behaves as a competitive inhibitor. The Km values for all-trans-retinol (2-3 M), estimated in the absence of detergent, are 10-fold lower than those obtained at the usual 0.02% Tween 80. This suggests a contribution of ADH in retinoid metabolism more relevant than previously expected. However, Tween 80 stabilizes retinoids in water solution and provides a reliable and reproducible assay, suitable for comparing different ADHs and different retinoid substrates.

Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: imaging; phosphorescence; eye; retina. Includes bibliographical references (p. 50-55).

Thesis (Ph. D., Neuroscience)--University of Idaho, October 2009. / Major professor: Deborah L. Stenkamp. Includes bibliographical references. Also available online (PDF file) by subscription or by purchasing the individual file.

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 116-130). Also available online.

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 116-130). Also available in print.

Thesis (Ph. D.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 106-128).

Age-related macular degeneration (AMD) causes vision impairment which is not recoverable under existing treatment options. It has been a major leading cause of blindness in the aged population. To ameliorate the self-care ability for AMD patients, educational interventions to mediate negative impacts of the disease on quality of life have become a research interest. Current practice in the proposed Hong Kong setting, Elderly Health Centre A and Elderly Health Centre B, depends on nurses giving general advice which is lack of scientific support and non-specific to AMD. Purpose of this dissertation is to translate the best evidence to practice for improving the care of older adults with AMD in the proposed setting. Evidences showed that self-management education programmes were effective in improving emotional distress and self-efficacy. Electronic searches located 9 relevant RCTs of high level and methodologically strong evidences. Data was extracted into tables of evidence. Data summary and synthesis was presented. Assessment on the implementation potential indicated that the SEP was worth to try in the local setting. Twelve recommendations for the practice guidelines of SEP were presented and a communication process to facilitate the change in a top-down approach was introduced. A pilot study plan in Centre A followed by a main study in Centre A and Centre B was presented. A total of 98 elderly patients with AMD will be recruited as 10 SEP groups. Approximately 1.8 years will be used to finish the main study. Outcomes will be measured at the 6th week follow-up. ‘Emotional distress’ will be measured as primary outcome and ‘self-efficacy’ will be measured as secondary outcome. ‘Client satisfaction’, ‘staff satisfaction’ and the ‘utilization rate of the innovation’ will also be assessed in evaluation. A two-tailed paired (one-sample) t-test will be adopted for analysis, with a 95% confidence interval. The basis for effectiveness for the outcome measurements and basis for adoption of the clinical guidelines were stated. Adoption of the developed guidelines in the local setting will optimistically improve the substantial clinical outcomes for AMD patients, mediating the negative impacts of vision impairment or vision loss on their quality of life. / published_or_final_version / Nursing Studies / Master / Master of Nursing

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