A expressão do receptor de potencial receptor transiente, vanilóide 1 (TRPV1) começa desde estágios pré-sinaptogênicos da retina. O bloqueio farmacológico desse receptor nesse período diminui a apoptose fisiológica, havendo possível envolvimento da sinalização de MAP quinases. Na retina do animal adulto, observamos que a expressão de TRPV1 é amplamente difundida, albergando neurônios, células endoteliais e células da microglia. A ativação dos receptores TRPV1 é potencialmente citotóxica, e os mecanismos que podem estar envolvidos incluem a liberação de glutamato, a excitotoxicidade e o estresse nitrosativo. Evidenciamos que a lesão prévia de células ganglionares sensibiliza o tecido retiniano à citotoxicidade mediada pela estimulação de TRPV1. Porém, o bloqueio de TRPV1, tanto in vivo quanto in vitro, não inibiu a morte de células ganglionares axotomizadas. Esses dados sugerem que o receptor TRPV1 participa da modulação de diversos processos fisiopatológicos na retina. / TRPV1 expression in the developing retina begins before retinal sinaptogenesis. TRPV1 blockade reduced the normal apoptosis in this period, and MAPK signaling seems to be involved in this process. In the adult retina, TRPV1 are expressed in neuronal, endothelial and microglial cells. The activation of those receptors is potentially cytotoxic, and glutamate release and further excitotoxicity and nitrosative stress might be also involved. Axotomized retinal ganglion cells were sensitized to TRPV1 citotoxicity, but TRPV1 antagonism, both in vitro and in vivo, did not reduce the loss of ganglion cell after axotomy. Our results suggest that TRPV1 receptors are involved in synaptic function and homeostatic control in the retina. Moreover, TRPV1 seems to be indirectly involved in cellular degeneration that follows the section of retinal ganglion cell axons.

Abstract Glaucoma is a progressive neuropathy of the optic nerve. It causes degeneration of ganglion cell axons resulting in defects in the retinal nerve fibre layer (RNFL) and characteristic changes in the optic nerve head (ONH). The Heidelberg Retina Tomograph (HRT) is a confocal scanning laser imaging device, which measures the topography of the ONH and the adjacent RNFL. To quantify the measurements of the ONH topography, various stereometric parameters are calculated. The change in the stereometric parameters of the HRT was studied in 34 eyes with glaucomatous progression in RNFL photographs and 34 eyes without progression. The change in only one stereometric parameter, the cup shape measure, showed a statistically significant correlation with the progression of the RNFL defect. An optimised change in the best three-parameter combination had 77% sensitivity and 79% specificity for progression. The change in the stereometric parameters was compared in 51 eyes with glaucomatous progression in stereoscopic ONH photographs and 425 eyes without progression. The parameters having the best correlation with progression include cup:disc area ratio, vertical cup:disc ratio, cup volume and rim area. The parameter with the largest area under the receiver operating characteristics curve (0.726) was the vertical cup:disc ratio. A change of 0.007 in the vertical cup:disc ratio had a sensitivity of 80% and a specificity of 65% for progression. The factors having the most significant effect on the sensitivity and specificity of the stereometric parameters for progression were the reference height difference and the mean topography standard deviation, indicating image quality. The change in image quality and age also showed a consistent, but variably significant influence on all parameters tested. Exercise was associated with an increase in variance in 17 of the 18 stereometric parameters. In conclusion, the change in the stereometric parameters provides useful information on ONH topography, especially when image quality is excellent. However, the evaluation of glaucomatous progression should not rely solely on the stereometric parameters of the HRT.

Visual field tests are routinely used for the detection and management of glaucoma. This thesis focuses on monitoring the vigilance during perimetry with pupil dynamics (pupillary movements, blinks) in glaucoma patients and the performance of using subsets of standard test patterns at detecting glaucomatous field loss. It describes the spatial pattern of visual field changes in diabetic retinopathy patients after treatment and the usage of multispectral imaging of the optic nerve head in glaucoma patients.The first investigation evaluated the use of pupillary parameters (pupil size and amplitude of pupillary oscillations) to monitor vigilance during perimetry in comparison to electroencephalography. A significant correlation was observed between the decreased pupil size and increased slow brain activities (theta and alpha). The inter-test threshold variability correlated with the pupil miosis.Another investigation explored blinks during a perimetric test and their relationship to the variability of threshold sensitivity in glaucoma patients. A wide range of blink frequencies was observed in glaucoma patients during perimetry and the timing of blinks was correlated with the stimuli presentations when they were supra-threshold. No significant relationship was observed between the threshold sensitivity variability and blink parameters (frequency, duration and microsleep numbers).The third investigation evaluated the use of subset of the 24-2 visual field test pattern at detecting glaucomatous field loss. A high sensitivity and specificity was observed when using subsets of the 24-2 pattern and test locations optimized by the positive predictive values showed a better performance than the test locations in random sequences.With the usage of a self-organized mapping method, nine spatial patterns of visual field loss in untreated diabetic retinopathy patients were classified. After laser treatment, a significant improvement on the spatial patterns of field loss and global indices was found.In the multispectral imaging study, the haemoglobin dependent differential light absorption (DLA) properties of the glaucomatous optic nerve head was evaluated with multispectral imaging. Change of DLA after medical hypotensive treatment was graded by five experts and no difference was observed in most of the patients.

The aim of this thesis was to design and implement the interactive Java applet used for topography 3D optic nerve head visualization. Primary purpose of the 3D vizualization is ophthalmology, especially for diagnosis of glaucoma. More over should serve as a training material, which enables to study the transformation of 2D figures to 3D model and to test the effects of adjustments and regulations to imaging of the model in 3D space. Two program versions were designed in this work using the development system NetBeans version 5.5. Their final realization is implemented as .html application working in web browser window. First version of the designed applet is simple intuitive application with several default settings, so that the figure is opened automatically to 3D model. Subsequently, the applet enables to set the size of the image, 3D depth of the image, smoothing of the surface and selection of monochrome or coloured image. The second version is the extension of the first version of the designed applet, and provides the possibility to display x, y, z axis, depiction of the 3D model surface by dots, curves or grid, and illumination of the surface. Software was tested on available topographic data acquired by HRT equipment and in different web browsers. Technical documentation and user’s manual are also involved in this thesis.

This work is focused on detection of loss in nerve fibre layer on colour pictures of retina, witch are makes by fundus camera. It describe every simple objects of retina, optic nerve head, macula lutea and vascular bed. It detect optic nerve head and his near area, witch is general for detection of breakdownds. It use several metodes of picture adjusting for picture elaboration and objects detection (segmentation, thresholding, enhancement, hough transformation ). The detection of loss in nerve fibre layer is based on comparing of statistic parameters ( average, standart deviation, skewness coefficient and kurtosis coefficient histogram, entropy ) in choosed areas with and withou destruction of nerve layers. Vascular bed have badwatsh on results, cause of this we using hand choosing of essay.

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The general organization and 'function of the vertebrate visual system has been under Investigation since the late nineteenth century (Gudden, lS7Qa, Gudden, 1870b). The organization of optic tracts and subcortical optic centers for the majority of vertebrates studied are found to be similar in both structure and function (Gudden, 1870a, Gudden, 1870b, Minkowski, 1913» Minkowski, 1920, and Lashley, 193^a). The sense organ, the eye, contains specific photoreceptor cells designated as either retinal rods or retinal cones. These two types of retinal cells possess an ability to convert light quanta into nerve impulses. The nerve impulses are transmitted via the optic nerves, and optic tracts to four major anatomical areas of Initial synapse within the central nervous system; the lateral geniculate bodies (for both the dorsal and ventral, nucleus) , the stratum optlcum of the superior colliculi, tlie pretectum, and the cuter cellular layers of the visual cortex located on either edge of the calcarine fissure of the temporal lobes (see Figures 1, 2, and 3)-

yes / Purpose: Inter-individual variance in optic nerve head (ONH) position, axial length and location of the temporal raphe suggest that customizing mapping between visual field locations and optic nerve head sectors for individuals may be clinically useful. Here we quantify the proportion of the population predicted to have structure-function mappings that markedly deviate from “average”, and thus would benefit from customized mapping. Design: Database study and case report Participants: Population database of 2836 eyes from the Beijing Eye Study; single case report of an individual with primary open angle glaucoma Methods: Using the morphometric fundus data of the Beijing Eye Study on 2836 eyes and applying a recently developed model based on axial length and ONH position relative to the fovea, we determined for each measurement location in the 24-2 Humphrey visual field the proportion of eyes for which, in the customized approach as compared to the generalized approach, the mapped ONH sector was shifted into a different sector. We determined the proportion of eyes for which the mapped ONH location was shifted by 15°, 30° or 60°. Main outcome measures: Mapping correspondence between locations in visual field space to localized sectors on the optic nerve head Results: The largest inter-individual differences in mapping are in the nasal step region where the same visual field location can map to either the superior or inferior ONH depending on other anatomical features. For these visual field locations, approximately 12% of eyes showed a mapping opposite to conventional expectations. Conclusions: Anatomically customised mapping shifts the map markedly in approximately 12% of the general population in the nasal step region where visual field locations can map to the opposite pole of the ONH than conventionally considered. Early glaucomatous damage commonly affects this region, hence individually matching structure to function may prove clinically useful for the diagnosis and monitoring of progression within individuals. / Australian Research Council Linkage Project 130100055 (industry partner, Heidelberg Engineering, GmBH, Germany).

Purpose: The purpose of this study was to investigate the role of the vasculature and immune system in models of glaucoma. Vascular changes have been implicated in glaucoma. As well there is mounting evidence that the immune system plays a role in the disease. It is my hypothesis that the vasculature and immune system play a role in the retinal response to injury in models of glaucoma. Methods: Immunohistochemistry, in vivo retinal imaging (Bright field, fluorescent, optical coherence tomography), Slit2 injections and Evan’s blue labeling were used to investigate vascular and immune changes associated with retinal ganglion cell death after optic nerve crush up to 28 days after injury. Histology, immunohistochemistry, and intravascular labeling were utilized to investigate the role of the vascular degeneration and the systemic immune response to elevated intraocular pressure in 8-16 week old AP-2β Neural Crest Cell Knockout (AP-2β NCC KO) mice. Results: The vascular and immune responses to optic nerve crush were not found to play a significant role in the response to retinal ganglion cell death. Conversely the role of vascular degeneration and immune cell recruitment to the retinas of AP-2β NCC KO mice demonstrated that these factors played a significant role in the retinal response to injury. Conclusion: The vasculature and immune system play a varied role in the response to retinal injury and neurodegeneration depending on the model being studied. The vascular and immune changes were of minimal significance in acute optic nerve crush injury. On the other hand, the chronic injury associated with elevated intraocular pressure in AP-2β NCC KO mice was associated with significant vascular degeneration and systemic immune cell infiltration. / Thesis / Doctor of Philosophy (PhD)