Information management system study results. Volume 1: IMS study results

The information management system (IMS) special emphasis task was performed as an adjunct to the modular space station study, with the objective of providing extended depth of analysis and design in selected key areas of the information management system. Specific objectives included: (1) in-depth studies of IMS requirements and design approaches; (2) design and fabricate breadboard hardware for demonstration and verification of design concepts; (3) provide a technological base to identify potential design problems and influence long range planning (4) develop hardware and techniques to permit long duration, low cost, manned space operations; (5) support SR&T areas where techniques or equipment are considered inadequate; and (6) permit an overall understanding of the IMS as an integrated component of the space station

Electronic Devices for the Combination of Electrically Controlled Drug Release, Electrostimulation, and Optogenetic Stimulation for Nerve Tissue Regeneration

[ES] La capacidad de las células madre para proliferar formando distintas células especializadas les otorga la potencialidad de servir de base para terapias efectivas para patologías cuyo tratamiento era inimaginable hasta hace apenas dos décadas. Sin embargo, esta capacidad se encuentra mediada por estímulos fisiológicos, químicos, y eléctricos, específicos y complejos, que dificultan su traslación a la rutina clínica. Por ello, las células madre representan un campo de estudio en el que se invierten amplios esfuerzos por parte de la comunidad científica. En el ámbito de la regeneración nerviosa, para modular su desarrollo y diferenciación el tratamiento farmacológico, la electroestimulación, y la estimulación optogenética son técnicas que están consiguiendo prometedores resultados. Es por ello por lo que en la presente tesis se ha desarrollado un conjunto de sistemas electrónicos para permitir la aplicación combinada de estas técnicas in vitro, con perspectiva a su aplicación in vivo. Hemos diseñado una novedosa tecnología para la liberación eléctricamente controlada de fármacos. Esta tecnología está basada en nanopartículas de sílice mesoporosa y puertas moleculares de bipiridina-heparina. Las puertas moleculares son electroquímicamente reactivas, y encierran los fármacos en el interior de las nanopartículas, liberándolos ante un estímulo eléctrico. Hemos caracterizado esta tecnología, y la hemos validado mediante la liberación controlada de rodamina en cultivos celulares de HeLa. Para la combinación de liberación controlada de fármacos y electroestimulación hemos desarrollado dispositivos que permiten aplicar los estímulos eléctricos de forma configurable desde una interfaz gráfica de usuario. Además, hemos diseñado un módulo de expansión que permite multiplexar las señales eléctricas a diferentes cultivos celulares. Además, hemos diseñado un dispositivo de estimulación optogenética. Este tipo de estimulación consiste en la modificación genética de las células para que sean sensibles a la radiación lumínica de determinada longitud de onda. En el ámbito de la regeneración de tejido mediante células precursoras neurales, es de interés poder inducir ondas de calcio, favoreciendo su diferenciación en neuronas y la formación de circuitos sinápticos. El dispositivo diseñado permite obtener imágenes en tiempo real mediante microscopía confocal de las respuestas transitorias de las células al ser irradiadas. El dispositivo se ha validado irradiando neuronas modificadas con luz pulsada de 100 ms. También hemos diseñado un dispositivo electrónico complementario de medida de irradiancia con el doble fin de permitir la calibración del equipo de irradiancia y medir la irradiancia en tiempo real durante los experimentos in vitro. Los resultados del uso de los bioactuadores en procesos complejos y dinámicos, como la regeneración de tejido nervioso, son limitados en lazo abierto. Uno de los principales aspectos analizados es el desarrollo de biosensores que permitiesen la cuantización de ciertas biomoléculas para ajustar la estimulación suministrada en tiempo real. Por ejemplo, la segregación de serotonina es una respuesta identificada en la elongación de células precursoras neurales, pero hay otras biomoléculas de interés para la implementación de un control en lazo cerrado. Entre las tecnologías en el estado del arte, los biosensores basados en transistores de efecto de campo (FET) funcionalizados con aptámeros son realmente prometedores para esta aplicación. Sin embargo, esta tecnología no permitía la medición simultánea de más de una biomolécula objetivo en un volumen reducido debido a las interferencias entre los distintos FETs, cuyos terminales se encuentran inmersos en la solución. Por ello, hemos desarrollado instrumentación electrónica capaz de medir simultáneamente varios de estos biosensores, y la hemos validado mediante la medición simultánea de pH y la detección preliminar de serotonina y glutamato.[CA] La capacitat de les cèl·lules mare per a proliferar formant diferents cèl·lules especialitzades els atorga la potencialitat de servir de base per a teràpies efectives per a patologies el tractament de les quals era inimaginable fins fa a penes dues dècades. No obstant això, aquesta capacitat es troba mediada per estímuls fisiològics, químics, i elèctrics, específics i complexos, que dificulten la seua translació a la rutina clínica. Per això, les cèl·lules mare representen un camp d'estudi en el qual s'inverteixen amplis esforços per part de la comunitat científica. En l'àmbit de la regeneració nerviosa, per a modular el seu desenvolupament i diferenciació el tractament farmacològic, l'electroestimulació, i l'estimulació optogenética són tècniques que estan aconseguint prometedors resultats. És per això que en la present tesi s'ha desenvolupat un conjunt de sistemes electrònics per a permetre l'aplicació combinada d'aquestes tècniques in vitro, amb perspectiva a la seua aplicació in vivo. Hem dissenyat una nova tecnologia per a l'alliberament elèctricament controlat de fàrmacs. Aquesta tecnologia està basada en nanopartícules de sílice mesoporosa i portes moleculars de bipiridina-heparina. Les portes moleculars són electroquímicament reactives, i tanquen els fàrmacs a l'interior de les nanopartícules, alliberant-los davant un estímul elèctric. Hem caracteritzat aquesta tecnologia, i l'hem validada mitjançant l'alliberament controlat de rodamina en cultius cel·lulars de HeLa. Per a la combinació d'alliberament controlat de fàrmacs i electroestimulació hem desenvolupat dispositius que permeten aplicar els estímuls elèctrics de manera configurable des d'una interfície gràfica d'usuari. A més, hem dissenyat un mòdul d'expansió que permet multiplexar els senyals elèctrics a diferents cultius cel·lulars. A més, hem dissenyat un dispositiu d'estimulació optogenètica. Aquest tipus d'estimulació consisteix en la modificació genètica de les cèl·lules perquè siguen sensibles a la radiació lumínica de determinada longitud d'ona. En l'àmbit de la regeneració de teixit mitjançant cèl·lules precursores neurals, és d'interés poder induir ones de calci, afavorint la seua diferenciació en neurones i la formació de circuits sinàptics. El dispositiu dissenyat permet obtindré imatges en temps real mitjançant microscòpia confocal de les respostes transitòries de les cèl·lules en ser irradiades. El dispositiu s'ha validat irradiant neurones modificades amb llum polsada de 100 ms. També hem dissenyat un dispositiu electrònic complementari de mesura d'irradiància amb el doble fi de permetre el calibratge de l'equip d'irradiància i mesurar la irradiància en temps real durant els experiments in vitro. Els resultats de l'ús dels bioactuadors en processos complexos i dinàmics, com la regeneració de teixit nerviós, són limitats en llaç obert. Un dels principals aspectes analitzats és el desenvolupament de biosensors que permeteren la quantització de certes biomolècules per a ajustar l'estimulació subministrada en temps real. Per exemple, la segregació de serotonina és una resposta identificada amb l'elongació de les cèl·lules precursores neurals, però hi ha altres biomolècules d'interés per a la implementació d'un control en llaç tancat. Entre les tecnologies en l'estat de l'art, els biosensors basats en transistors d'efecte de camp (FET) funcionalitzats amb aptàmers són realment prometedors per a aquesta aplicació. No obstant això, aquesta tecnologia no permetia el mesurament simultani de més d'una biomolècula objectiu en un volum reduït a causa de les interferències entre els diferents FETs, els terminals dels quals es troben immersos en la solució. Per això, hem desenvolupat instrumentació electrònica capaç de mesurar simultàniament diversos d'aquests biosensors i els hem validat amb mesurament simultani del pH i la detecció preliminar de serotonina i glutamat.[EN] The stem cells' ability to proliferate to form different specialized cells gives them the potential to serve as the basis for effective therapies for pathologies whose treatment was unimaginable until just two decades ago. However, this capacity is mediated by specific and complex physiological, chemical, and electrical stimuli that complicate their translation to clinical routine. For this reason, stem cells represent a field of study in which the scientific community is investing a great deal of effort. In the field of nerve regeneration, to modulate their development and differentiation, pharmacological treatment, electrostimulation, and optogenetic stimulation are techniques that are achieving promising results. For this reason, we have developed a set of electronic systems to allow the combined application of these techniques in vitro, with a view to their application in vivo. We have designed a novel technology for the electrically controlled release of drugs. This technology is based on mesoporous silica nanoparticles and bipyridine-heparin molecular gates. The molecular gates are electrochemically reactive and entrap the drugs inside the nanoparticles, releasing them upon electrical stimulus. We have characterized this technology and validated it by controlled release of rhodamine in HeLa cell cultures. For combining electrostimulation and controlled drug release we have developed devices that allow applying the different electrical stimuli in a configurable way from a graphical user interface. In addition, we have designed an expansion module that allows multiplexing electrical signals to different cell cultures. In addition, we have designed an optogenetic stimulation device. This type of stimulation consists of genetically modifying cells to make them sensitive to light radiation of a specific wavelength. In tissue regeneration using neural precursor cells, it is interesting to be able to induce calcium waves, favoring the cell differentiation into neurons and the formation of synaptic circuits. The designed device enable the obtention of real-time images through confocal microscopy of the transient responses of cells upon irradiation. The device has been validated by irradiating modified neurons with 100 ms pulsed light stimulation. We have also designed a complementary electronic irradiance measurement device to allow calibration of the irradiator equipment and measuring irradiance in real time during in vitro experiments. The results of using bioactuators in complex and dynamic processes, such as nerve tissue regeneration, are limited in an open loop. One of the main aspects analyzed is the development of biosensors that would allow quantifying of specific biomolecules to adjust the stimulation provided in real time. For instance, serotonin secretion is an identified response of neural precursor cells elongation, among other biomolecules of interest for the implementation of a closed-loop control. Among the state-of-the-art technologies, biosensors based on field effect transistors (FETs) functionalized with aptamers are promising for this application. However, this technology did not allow the simultaneous measurement of more than one target biomolecule in a small volume due to interferences between the different FETs, whose terminals are immersed in the solution. This is why we have developed electronic instrumentation capable of simultaneously measuring several of these biosensors, and we have validated it with the simultaneous pH measurement and the preliminary detection of serotonin and glutamate.Monreal Trigo, J. (2023). Electronic Devices for the Combination of Electrically Controlled Drug Release, Electrostimulation, and Optogenetic Stimulation for Nerve Tissue Regeneration [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/19384

The Role of Non-Linearities in Visual Perception studied with a Computational Model of the Vertebrate Retina

Processing of visual stimuli in the vertebrate retina is complex and diverse. The retinal output to the higher centres of the nervous system, mediated by ganglion cells, consists of several different channels. Neurons in these channels can have very distinct response properties, which originate in different retinal pathways. In this work, the retinal origins and possible functional implications of the segregation of visual pathways will be investigated with a detailed, biologically realistic computational model of the retina. This investigation will focus on the two main retino-cortical pathways in the mammalian retina, the parvocellular and magnocellular systems, which are crucial for conscious visual perception. These pathways differ in two important aspects. The parvocellular system has a high spatial, but low temporal resolution. Conversely, the magnocellular system has a high temporal fidelity, spatial sampling however is less dense than for parvocellular cells. Additionally, the responses of magnocellular ganglion cells can show pronounced nonlinearities, while the parvocellular system is essentially linear. The origin of magnocellular nonlinearities is unknown and will be investigated in the first part of this work. As their main source, the results suggest specific properties of the photoreceptor response and a specialised amacrine cell circuit in the inner retina. The results further show that their effect combines in a multiplicative way. The model is then used to examine the influence of nonlinearities on the responses of ganglion cells in the presence of involuntary fixational eye movements. Two different stimulus conditions will be considered: visual hyperacuity and motion induced illusions. In both cases, it is possible to directly compare properties of the ganglion cell population response with psychophysical data, which allows for an analysis of the influence of different components of the retinal circuitry. The simulation results suggest an important role for nonlinearities in the magnocellular stream for visual perception in both cases. First, it will be shown how nonlinearities, triggered by fixational eye movements, can strongly enhance the spatial precision of magnocellular ganglion cells. As a result, their performance in a hyperacuity task can be equal to or even surpass that of the parvocellular system. Second, the simulations imply that the origin of some of the illusory percepts elicited by fixational eye movements could be traced back to the nonlinear properties of magnocellular ganglion cells. As these activity patterns strongly differ from those in the parvocellular system, it appears that the magnocellular system can strongly dominate visual perception in certain conditions. Taken together, the results of this theoretical study suggest that retinal nonlinearities may be important for and strongly influence visual perception. The model makes several experimentally verifiable predictions to further test and quantify these findings. Furthermore, models investigating higher visual processing stages may benefit from this work, which could provide the basis to produce realistic afferent input

Renewable Energy

Renewable Energy is energy generated from natural resources - such as sunlight, wind, rain, tides and geothermal heat - which are naturally replenished. In 2008, about 18% of global final energy consumption came from renewables, with 13% coming from traditional biomass, such as wood burning. Hydroelectricity was the next largest renewable source, providing 3% (15% of global electricity generation), followed by solar hot water/heating, which contributed with 1.3%. Modern technologies, such as geothermal energy, wind power, solar power, and ocean energy together provided some 0.8% of final energy consumption. The book provides a forum for dissemination and exchange of up - to - date scientific information on theoretical, generic and applied areas of knowledge. The topics deal with new devices and circuits for energy systems, photovoltaic and solar thermal, wind energy systems, tidal and wave energy, fuel cell systems, bio energy and geo-energy, sustainable energy resources and systems, energy storage systems, energy market management and economics, off-grid isolated energy systems, energy in transportation systems, energy resources for portable electronics, intelligent energy power transmission, distribution and inter - connectors, energy efficient utilization, environmental issues, energy harvesting, nanotechnology in energy, policy issues on renewable energy, building design, power electronics in energy conversion, new materials for energy resources, and RF and magnetic field energy devices

Organotypic hippocampal slice culture model of epileptogenesis : electrophisiological and molecular features

Tese de mestrado, Neurociências, Universidade de Lisboa, Faculdade de Medicina, 2014Introdução: As culturas organotípicas podem ser mantidas por longos períodos de incubação através do uso de dois meios de cultura: o meio Optimem, com soro de cavalo, e o meio Neurobasal, suplementado com B27. O soro contém substâncias indefinidas e em quantidades desconhecidas. O meio de cultura Neurobasal, por seu turno, é totalmente definido, o que permite um controlo preciso do ambiente extracelular das culturas. Porém, as propriedades funcionais das células mantidas em meio Neurobasal não são totalmente conhecidas. Além disso, neste meio as fatias desenvolvem atividade epileptiforme espontânea, que se assemelha com a epilepsia in vivo. Objectivo: O objectivo deste estudo é explorar as propriedades celulares e moleculares correlacionadas com a epileptogénese em culturas organotípicas de hipocampo. Metodologia: De forma a explorar os efeitos da remoção do soro nas culturas organotípicas, utilizaram-se duas condições: 1) fatias mantidas num meio com soro, 2) fatias mantidas num meio isento de soro. Avaliou-se a integridade das fatias, a morte celular, e as propriedades funcionais das células. Por fim, de modo a explorar as características correlacionadas com a epilepsia, em fatias mantidas num meio sem soro, avaliou-se a atividade epileptiforme, a ativação dos astrócitos e da microglia, bem como a transcrição das subunidades dos receptores do GABAA e da glicina. Resultados: Observou-se um aumento da excitabilidade das células piramidais de CA1 nas fatias mantidas num meio isento de soro, bem como uma diminuição da eficiência sináptica, sem afectar a integridade das fatias e a morte celular. Estes efeitos, ao longo do período de incubação, aumentam a vulnerabilidade e incidência da atividade epileptiform espontânea, tendo sido observado um progressivo aumento da prevalência da atividade ictal que acompanhou a ativação dos astrócitos e da microglia, bem como a alteração na expressão das subunidades dos receptores GABAA e da glicina. Conclusão: As culturas organotípicas de hipocampo são um modelo útil no estudo da epileptogénese, uma vez que desenvolvem características semelhantes às observadas na epilepsia in vivo.Introduction: Organotypic hippocampal slice cultures can be maintained for long periods of time in vitro using an Optimem horse serum-based medium, which contains unknown quantities of undefined substances, or using a chemically defined Neurobasal medium supplemented with B27. Neurobasal B27-supplemented allows precise control of extracellular environment and avoids the effects of unknown growth factors. However, the functional properties of these cells maintained in this serum-free medium were not yet fully known. Moreover, organotypic slices maintained Neurobasal medium develop spontaneous epileptiform activity that resembles in vivo epilepsy. Aim: The aim of this study is to explore the cellular and molecular correlates of epileptogenesis in organotypic hippocampal slice cultures. Methodology: In order to explore the effects of serum removal, slices were maintained in two different conditions: 1) serum-contain growth medium, 2) serum-free growth medium. Slice integrity, cell death, and functional properties were evaluated. Finally, using serum-free organotypic slice cultures as a model of epileptogenesis, epileptiform activity, astrogliosis and microglia activation, as well as GABAA and glycine receptor transcripts were assessed. Results: Serum removal increased cells excitability and decreased the synaptic efficiency of CA1 hippocampal pyramidal cells, without changing the slice integrity and cell death. These effects, throughout incubation period, lead to increased vulnerability and incidence of spontaneous epileptiform activity. Ictal-like activity becomes progressively more prevalent and overlaps the astrocyte and microglia activation, as well as the changes in GABAAR e GlyR subunits expression. Conclusion: Organotypic hippocampal slice cultures comprise a useful model of epileptogenesis. They develop many features correlated with epilepsy, and can be kept as “in vivo-like” using a defined culture medium

Investigation of the Functional Effects of Two Novel Ampakines in the CNS

The ionotropic glutamate AMPA ((R,S)-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor mediates the majority of excitatory transmission in the CNS. AMPA receptors play a crucial role in both basal neurotransmission and synaptic plasticity events (such as long-term potentiation, LTP). Compounds that ‘potentiate’ AMPA receptor function (‘Ampakines’) are known to positively modulate glutamatergic AMPA receptor-gated currents, by slowing the deactivation and desensitisation rate of the receptors, in the presence of the endogenous agonist glutamate. Ampakines have been shown to facilitate LTP induction, improve cognition, and as such have potential in the treatment of conditions such as depression and psychoses (schizophrenia). The main aim of this thesis was to investigate the functional actions of two novel Ampakines, Org 26576 and Org 24448, in the mouse brain. The studies described in this thesis were designed to address this and are outlined as follows: 1. Characterisation and validation of an in vivo semi-quantitative model of [14C]-2-deoxyglucose autoradiography in the C57Bl/6J mouse The first study sought to develop and characterise a model of [14C]-2-deoxyglucose autoradiography, to allow measurement of regional alterations in local cerebral glucose use (LCGU) in the mouse CNS. Following intraperitoneal injection of [14C]-2-deoxyglucose in C57Bl/6J mice, the radiolabelled brains were sectioned and exposed to x-ray film. The resultant autoradiograms were semi-quantitatively analysed for relative optical densities in predetermined regions of interest. The baseline LCGU values in different brain regions were found to be consistent with previously published data. The model was also able to replicate the effects of a well-characterised compound, the NMDA receptor antagonist MK-801 (0.5 mg/kg), in respect to functional cerebral changes. Characteristic effects such as prominent increases in LCGU in the limbic system, and decreases in the somatosensory cortex were reproduced in the model. Thus the semi-quantitative [14C]-2-deoxyglucose model was reproducible and accurate and thus could be further used to investigate the effects of the novel Ampakines, Org 26576 and Org 24448, on cerebral function. 2. Investigation into the effects of acute administration of the novel Ampakines Org 26576 and Org 24448 on functional activity in the murine cerebrum Following the establishment of the methodology, regional alterations in LCGU in response to the Ampakines Org 26576 and Org 24448 were investigated using [14C]-2-deoxyglucose autoradiography. Both Org 26576 and Org 24448 produced regionally selective, dose-dependent increases in LCGU in the mouse cerebrum when administered acutely (~1 hr). The compounds displayed similar yet functionally distinct profiles of activation, the highest levels of activation occurred in areas of the limbic system (hippocampus), sensory systems, and various nuclei (raphe nucleus). Their effects were blocked by pre-administration of the potent selective AMPA receptor antagonist, NBQX (10 mg/kg), which itself had minimal effects on LCGU. These data provide an anatomical basis for the cerebral activation induced by these compounds, which are directly AMPA receptor mediated. Areas activated also closely correlated with brain regions implicated in various psychiatric conditions, and as such is suggestive of a potential therapeutic benefit of these compounds in conditions such as depression and schizophrenia. 3. Investigation into the effects of chronic administration of the novel Ampakines Org 26576 and Org 24448 on functional activity, neurogenesis and receptor/signalling alterations in the murine cerebrum Following the demonstration that acute administration of Org 26576 and Org 24448 displayed regionally selective and dose-dependent alterations in LCGU, the effect of chronic administration of the Ampakines Org 26576 and Org 24448 on regional functional alterations ([14C]-2-deoxyglucose autoradiography), neurogenesis (BrdU labelling), and proteins levels (GluR, MAPK, LynK and CREB) (Western blot analysis) were investigated. Chronic administration (7 and 28 days) of Org 26576 (1 mg/kg) and Org 24448 (10 mg/kg) induced functional cerebral increases in the mouse cerebrum particularly in areas of the mesocorticolimbic system, which were not only rapid in onset, with significant effects visible after 7 days administration; but importantly were also persistent and long lasting. Chronic administration of the compounds had no significant effect on the level of neurogenesis or on the levels AMPA receptor subunits (GluR1,2,3), and signalling pathways (MAPK/LynK-CREB pathway), implicated in AMPA/Ampakine signalling, in the murine hippocampus. These data show that the Ampakines Org 26576 and Org 24448 when administered chronically can potentiate complex neural networks intimately associated with disease states, the effects of which are maintained over prolonged periods. There was no evidence that this involved an effect on neurogenesis or the MAPK/LynK-CREB signalling pathway. 4. Modulation of AMPA receptor kinetics by Org 26576 and Org 24448 influences synaptic plasticity in the murine hippocampus The ability of Org 26576 and Org 24448 to modify baseline kinetic properties of AMPA receptors and a paradigm of synaptic plasticity, LTP, in the mouse hippocampus was investigated using electrophysiology. Both Org 26576 and Org 24448 produced dose-dependant increases in fEPSP amplitude without affecting the half-width of responses, in acute hippocampal slices. Concentrations of both compounds, equating to functionally active levels witnessed in vivo, potentiated a stable form of LTP; whilst higher EC50 concentrations prevented the maintenance of LTP. These results are suggestive that Org 26576 and Org 24448 are effective in boosting the neural correlate of cognition, LTP, and may have potential in treating cognitive deficits, for example those associated with depression, schizophrenia or Alzheimer’s disease. The data presented in this thesis illustrate that the novel Ampakines Org 26576 and Org 24448 centrally modulate brain regions and circuitry intimately associated with conditions such as depression and schizophrenia (psychoses), with effects that are rapid in onset and persistent over chronic periods of administration. Specifically targeting the glutamatergic system through the use of these compounds may provide an innovative approach to treat various conditions that may be partly due to a compromise of normal excitatory glutamatergic neurotransmission

NASA thesaurus. Volume 3: Definitions

Publication of NASA Thesaurus definitions began with Supplement 1 to the 1985 NASA Thesaurus. The definitions given here represent the complete file of over 3,200 definitions, complimented by nearly 1,000 use references. Definitions of more common or general scientific terms are given a NASA slant if one exists. Certain terms are not defined as a matter of policy: common names, chemical elements, specific models of computers, and nontechnical terms. The NASA Thesaurus predates by a number of years the systematic effort to define terms, therefore not all Thesaurus terms have been defined. Nevertheless, definitions of older terms are continually being added. The following data are provided for each entry: term in uppercase/lowercase form, definition, source, and year the term (not the definition) was added to the NASA Thesaurus. The NASA History Office is the authority for capitalization in satellite and spacecraft names. Definitions with no source given were constructed by lexicographers at the NASA Scientific and Technical Information (STI) Facility who rely on the following sources for their information: experts in the field, literature searches from the NASA STI database, and specialized references

Retinal structure and function in age-related maculopathy

Age-related macular degeneration (AMD) is the principle cause of visual loss and blindness in the developed world. As new treatments and therapies are developed the need to better diagnose and then monitor outcomes of treatment has become more important. This thesis evaluates both structural and functional changes that occur in the early stage of AMD, known as age-related maculopathy (ARM), with the aim of determining their diagnostic potential. This thesis also explores the relationship between structural and functional parameters. Twenty four participants with ARM and 26 control participants were recruited. Retinal function was probed using four focal electroretinography (ERG) techniques: the focal cone ERG, focal flicker ERG, ERG photostress test and focal rod ERG. Long wavelength optical coherence tomography (OCT) was used to assess retinal structure, specifically retinal, choroidal and four intra-retinal layer thicknesses at 21 macular locations. These techniques were initially developed and optimised for the detection of AMD related changes. The ability of each parameter to diagnose ARM was assessed. Correlation and linear regression analyses were carried out to identify any relationships between retinal structure and function in healthy controls. Retinal thickness was reduced in participants with ARM at parafoveal locations (~2° eccentricity), but choroid thickness was unaffected. Diagnostically, focal ERG parameters provided better sensitivity and specificity to ARM than OCT measures, with the ERG photostress test providing the best diagnostic potential. No strong relationships were shown between any ERG parameter and any retinal or choroidal layer volume in control participants. Three ERG parameters were shown to be related to specific retinal features of ARM, but the strongest associations were between ERG photostress test recovery and focal cone ERG b-wave implicit time and a diagnosis of wet AMD in the contralateral eye. In conclusion the structural and functional parameters assessed appeared to provide independent information regarding disease status and severity. ERG parameters showed better diagnostic potential than OCT measures. The single most diagnostic parameter was the recovery time constant of the ERG photostress test.EThOS - Electronic Theses Online ServiceGBUnited Kingdo