This dissertation has two major parts; Analytical and Experimental. The analytical section contains a study using Finite Element Analysis of dynamic instrumentation to demonstrate stress reduction in adjacent level discs. The experimental section contains biomechanical testing of facet fusion allograft technique and finally a comparison between In Vivo and In Vitro intradiscal pressures to determine forces acting on Lumbar spine segment L4-L5. A comprehensive study of available data, technology and literature was done. Conventional fusion instrumentation is believed to accelerate the degeneration of adjacent discs due to the increased stresses caused by motion discontinuity. A three dimensional finite element model of the lumbar spine was obtained which simulated flexion and extension. Reduced stiffness and increased axial motion of dynamic posterior lumbar fusion instrumentation designs results in a ~10% cumulative stress reduction for each flexion cycle. The cumulative effect of this reduced amplitude and distribution of peak stresses in the adjacent disc may partially alleviate the problem of adjacent level disc degeneration. Traditionally a pedicle screw system has been used for fixation of the lumbar spine and this involves major surgery and recovery time. Facet fixation is a technique that has been used for stabilization of the lumbar spine. The cadaver segments were tested in axial rotation, combined flexion/extension and lateral bending. Implantation of the allograft dowel resulted in a significant increase in stiffness compared to control. Facet fusion allograft provides an effective minimally invasive method of treating debilitating pain caused by deteriorated facet joints by permanently fusing them. An In Vitro biomechanical study was conducted to determine the intradiscal pressure during spinal loading. The intradiscal pressures in flexion/extension, lateral bending and axial rotation was compared to In Vivo published data. There is no data that explains the actual forces acting on the spine during flexion, extension, lateral bending or axial rotation. The functional spinal units were tested in combined axial compression and flexion/extension, combined axial compression and lateral bending and combined axial compression and axial rotation using a nondestructive testing method. Overall, this study found a good correlation between In Vivo and In Vitro data. This can essentially be used to make physiological relation from experimental and analytical evaluations of the lumbar spine. It is important to know how much load needs to be controlled by an implant.

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Šiame darbe nagrinėta išsigimstanti dalinių išvestinių diferencialinių lygčių sistema su laipsniniu eilės išsigimimu. Rasti sistemos sprendiniai yra analizinės funkcijos išsigimimo daugdarų taškų aplinkose. Sprendiniai išskleisti laipsninėmis eilutėmis, kintamojo pagal kurį išsigimsta sistemos eilė laipsniais. / In this work, there was analyzed the system of partial differential equations with gradual degeneration of row. There were found the solutions of analytical function in manifold point environments. The solutions are expanded by gradual lines, by variable where system number of degrees degenerates.

The Royal College of Surgeons (RCS) rat was used as a model of human retinal degenerative disease, and for studying the efficacy of cell transplanation treatments. In order to characterize the spatial vision of the RCS strain, the visual acutiy and contrast sensitivity of adult non-dystrophic RCS rats was measured. The acuity and contrast sensitivity of these rats was normal. The acuity of dystrophic RCS rats was alos characterized to determine how photoreceptor degeneration affects vision. These rats progressively lost visual acuity from one month of age until elevn months of age when they were judged to be blind. The degeneration of vision in these animals was more protacted than would be predicted from previous anatomical and electrophysiological measures. Subretinal transplantation of human-derived Retinal Pigment Epithelial (RPE) cells and human Schwann cells into the dystrophic RCS rat significantly delayed the loss of visual acuity. These studies show that cell transplantation may be a viable method of limiting loss of vision in humans with retinal degenerative blinding diseases. / vii, 77 leaves ; 29 cm.

The established model used for evaluating potential therapies for retinal disease has significant limitations. A new model is proposed to account for these limitations: the visual adaptation model. The visual adaptation model was developed to provide a novel approach for testing potential treatments for retinal disease, and the work in this thesis provides empirical support for this model. Specifically, we evaluated two potential therapies for retinal degenerative disease and examined their effects on vision and retinal anatomy. In addition, the profile of retinal reorganization and its functional correlates were examined in RCS rats and transgenic rats which express a rhodopsin mutation; however, immunohistological work targeted one specific line (S334ter-4). Collectively, these studies provide evidence that supports the retinal adaptation model. These studies also provide a novel view of retinal and visual function in retinal disease which should be considered when evaluating treatments involving retinal degeneration. / xvii, 205 leaves : ill. ; 29 cm. --

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Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. Due to the inadequacy of current pharmacotherapies, novel molecular targets must be sought as potential therapeutic candidates. Furthermore, there is a need for more efficient and cost-effective animal models of this pathology in order to accelerate in vivo investigations. / Our laboratory is in possession of human choroidal neovascular membranes which we examined for expression of cyclooxygenase (COX)-2. This expression was characterized in retinal pigment epithelial, vascular endothelial, and fibroblast cells and correlated with patient age. We also looked at the feasibility of creating a rabbit laser-injury model to adequately mimic human neovascular AMD. / Our results suggest that anti-COX-2 therapies may be beneficial to some patients with neovascular AMD. Moreover, there is strong potential for the development of clinically relevant choroidal neovascularization in rabbits using the laser-injury technique. This approach may yield a novel, cost-effective AMD model.

Age-related macular degeneration (AMD) is a principal cause of blindness in the United States and other industrialized nations. An estimated 10 million Americans are afflicted with AMD, which is comparable in scope to the 12 million living with cancer, or the 5 million with Alzheimer’s disease. The prevalence of AMD steadily increases with age, affecting 2% of the population at age 40, and one in four people by age 80. For reasons that are not fully understood, AMD is more common in lightly-pigmented and female populations. Treatment of AMD is largely an unmet need: There are no FDA approved therapies except for a small percentage of individuals with end-stage disease. This dissertation investigates the mechanisms of AMD pathogenesis and offers insight into novel therapeutic strategies for this disease.

A high speed, high resolution spectral domain optical coherence tomography (SD-OCT) system was used to study in-vivo early morphological changes and optical nerve head (ONH) blood flow in the Long Evans rat retina, induced by administration of sodium iodate (NaIO3). Linear and circular scanned OCT images were acquired at the same location in the retina from healthy control rats and from rats injected with 40mg/kg of NaIO3 solution at 1, 3, 6 12, 24, 72 and 168 hours post drug administration. Morphological OCT images showed changes in the optical reflectance and layer thickness of the photoreceptor IS and OS. The formation of a new low reflective layer between the photoreceptor OS and the RPE was observed in all tested rats. This new layer appeared as early as 1 hour, increased in thickness after 6 hours, and disappeared by 12 hours post NaIO3 injection. The low optical reflectance and the dynamics of this new layer suggest that it was most likely fluid accumulation. Comparison with H&E stained histological sections and IgG immunohistochemistry revealed minimal photoreceptor OS cell swelling at hour 1, detachment of the OS from the RPE by hour 3, and breaking of the blood-retina barrier with significant fluid accumulation by hour 6 post NaIO3 injection. The Doppler Optical Micro-Angiography (DOMAG) algorithm was used to carry out quantitative analysis of the ONH blood flow. Estimation of flow rate on each ONH vessel was done by measurements of the Doppler angle, vessel size and the axial velocity. This study has demonstrated that the capability of UHR-OCT to study optical reflectance and layer thickness changes, rearrangement and detachment of the photoreceptor OS and RPE layers, together with flow rate estimation of retinal blood vessels. Therefore, it can serve as markers in future non-invasive, in-vivo studies of disease or drug induced retinal degeneration in ophthalmic research.