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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
121

Retinal ganglion cells vulnerability in a rat glaucoma model /

Lau, Hoi-shan, Flora. January 2005 (has links)
Thesis (M. Med. Sc.)--University of Hong Kong, 2005.
122

Factores asociados al éxito quirúrgico de la facotrabeculectomía en pacientes atendidos en el Hospital Nacional Guillermo Almenara Irigoyen. 2011-2013

Alvaro Tambra, Wendy Carola January 2015 (has links)
El documento digital no refiere un asesor / Publicación a texto completo no autorizada por el autor / Identifica los factores asociados al éxito quirúrgico de la facotrabeculectomía en pacientes con glaucoma y catarata atendidos en el servicio de oftalmología del Hospital Nacional Guillermo Almenara Irigoyen en el periodo comprendido entre enero del 2011 a diciembre del 2013. Se realiza un estudio observacional, descriptivo, retrospectivo, de casos y controles. Se revisan 73 historias clínicas de los pacientes con diagnóstico con glaucoma y catarata a quienes se les realiza facotrabeculectomía, en el periodo que correspondió al estudio. El 63% son mujeres y el 37% varones. La media de la edad es de 73,9+/-6,1 años con una mínima de 60 años y una máxima de 92 años. El tipo de glaucoma de mayor frecuencia es el glaucoma a ángulo abierto (75,3%).El 84,9% de los pacientes presentan catarata ++. El 43,8% presenta relación copa disco 0,6. Encontramos una diferencia significativa de la presión intraocular entre la presión preoperatoria y post operatoria (25,47 versus 13,66) (P<0,05). La tasa de éxito de los pacientes con glaucoma y catarata sometidos a facotrabeculectomía es del 98,6%, observándose que el éxito parcial es del 34,2%, y el éxito absoluto es del 64,4%. La complicación temprana postoperatoria de mayor frecuencia es la hipotensión (19,2%), y la tardía de mayor frecuencia es la hipertensión (15,1%). La media de la edad de los pacientes cuyo resultado es un éxito parcial es de 73,36+/-5,6 años, y de los pacientes con éxito absoluto es de 74,3+/-6,9 años. Concluye que los factores asociados al éxito quirúrgico de la facotrabeculectomía en pacientes con glaucoma y catarata son el sexo, tipo de glaucoma, tipo de catarata, y la ausencia de complicaciones. Existe una mayor frecuencia de pacientes del sexo femenino, mayores de 70 años, con glaucoma moderado y catarata ++. Se evidencia variaciones estadísticamente significativas de la PIO y del número de medicamentos entre el pre y post operatorio. La tasa de éxito de los pacientes con glaucoma y catarata sometidos a facotrabeculectomía es del 98,6%. La complicación temprana postoperatoria de mayor frecuencia es la hipotensión, y la complicación tardía de mayor frecuencia es la hipertensión. / Trabajo académico
123

Estudo da pressão intra-ocular em pacientes normais na cidade de Florianópolis

Dalmoro, Gladimir January 2003 (has links)
Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em Ciências Médicas. / Made available in DSpace on 2012-10-20T13:33:50Z (GMT). No. of bitstreams: 0 / Objetivo: Avaliar o comportamento da pressão intra-ocular (PIO) de 1.530 pacientes, normais do ponto de vista oftalmológico, de ambos os sexos, com idade entre 40 e 69 anos, da cidade de Florianópolis.
124

Efeito do cloridrato de dorzolamida a 2%, maleato de timol a 0,5% e associação de ambos na pressão intra-ocular: estudo experimental em cães

Borges, Alessandra Gonçalves [UNESP] January 2004 (has links) (PDF)
Made available in DSpace on 2014-06-11T19:23:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2004Bitstream added on 2014-06-13T19:30:13Z : No. of bitstreams: 1 borges_ag_me_botfmvz.pdf: 619936 bytes, checksum: 26f3dbd1632fca5d2ec5d73fee61d030 (MD5) / Dentre as doenças oculares diagnosticadas no cão, o glaucoma reveste-se de singular importância, como afecção potencial causadora de cegueira. O aumento da pressão intra-ocular (PIO) é o fator de risco primário para o desenvolvimento da neuropatia óptica glaucomatosa canina. A dorzolamida e o timolol, fármacos utilizados para o tratamento do glaucoma, reduzem a PIO pela diminuição da produção do humor aquoso, embora utilizem diferentes mecanismos de ação. O objetivo do trabalho foi avaliar o efeito do cloridrato de dorzolamida 2%, maleato de timolol 0,5% e da combinação de ambos na pressão intra-ocular de cães normais e verificar possíveis alterações na PIO do olho contra-lateral sem tratamento. Foram utilizados 60 cães, distribuídos em três grupos (G) aleatórios de 20 animais. Cada grupo recebeu tratamento tópico no olho esquerdo com timolol 0,5% (GT), dorzolamida 2% (GD) ou a combinação, timolol 0,5% e dorzolamida 2% (GTD). Em todos os grupos, a mensuração da PIO foi realizada utilizando-se tonômetro de aplanação (Tonopen). As medidas foram realizadas, em ambos os olhos, uma hora antes e uma, duas, quatro, seis e oito horas após a instilação de uma gota do colírio no olho esquerdo. No olho tratado percentual de redução máxima da associação timolol/dorzolamida foi numericamente superior (27%) comparado ao timolol (21,9%) e dorzolamida (22,4%) quando utilizados como monoterapia. O olho não tratado apresentou uma redução significativa da PIO, sendo que a redução máxima para o GT foi de 7%, para o GD de 13,8% e para o GTD de 13,6%. A dorzolamida e a associação timolol/dorzolamida promoveram uma ação redutora maior, após uma e seis horas da sua instilação no olho tratado. A administração tópica do timolol 0,5%, dorzolamida a 2% como monoterapia e a associação fixa destes fármacos resultou na redução significativa da PIO de cães clinicamente normais. / Glaucoma is one of the most important ocular diseases in the dog. Increased intraocular pressure (IOP) is the major risk factor for the development of glaucoma. Dorzolamide and timolol are drugs used for the treatment of glaucoma. Both drugs modify aqueous humor outflow by different mechanisms, resulting in decreased IOP. The aim of this work was to evaluate the efficacy of dorzolamide hydrochloride, timolol maleate and the combination of both drugs on IOP of healthy dogs. Sixty adult dogs were randomly and equally assigned to three groups (n = 20 per group). Each group received topical treatment in the left eye with 0,5% timolol, 2% dorzolamide or the combination (0,5% timolol / 2% dorzolamide). IOP measurements were made using aplanation tonometry (Tono-pen) after local instillation of 0,5% proparacaine in he both eyes. Measurements were performed 1 hour before (baseline) instillation of a single drop of the test drugs in the left eye, and at 1, 2, 4, 6 and 8 hours after treatment. Similar measurements were also performed in the right eye (nontreated eye). In the nontreated eye, IOP decreased over time, with a maximum decrease from baseline of 7%, 13,8% and 13,6% in the timolol, dorzolamide e timolol/dorzolamide groups, respectively. In the treated eye, there was a greater reduction in IOP for the combination (27% maximum decrease from baseline) when compared with timolol (21,9%) and dorzolamide (22,4%) groups. Dorzolamide and timolol/dorzolamide caused greater decreases in IOP at 1 and 6 hours after drug instillation. It was concluded that 0,5% timolol, 2% dorzolamide and the combination of these drugs are effective in reducing IOP in healthy dogs.
125

Pico e flutuação da pressão intra-ocular : comparação entre curva tensional diária e teste de sobrecarga hídrica e comparação entre 2 testes de sobrecarga hídrica em horários diferentes /

Addad, Mariluci Tosi. January 2010 (has links)
Resumo: Comparar pico e flutuação de pressão intra-ocular (PIO) entre curva tensional diária e teste de sobrecarga hídrica, detectar os horários de pico de PIO, comparar os valores da PIO nos horários das 6 horas da manhã deitado e sentado. 30 olhos direitos de 30 pacientes portadores de glaucoma primário de ângulo aberto (GPAA) ou hipertensão ocular (HO), foram submetidos à curva tensional diária de 24 horas (CTD) e teste de sobrecarga hídrica (TSH). Foram avaliados: pico (maior valor da PIO durante a CTD e TSH ) e flutuação (maior valor da PIO menos o menor valor da PIO durante o CTD e TSH). A PIO foi avaliada, com tonômetro de aplanação de Goldmann às 9, 12, 15, 18, 21, 24 e 6h, com paciente sentado. As medidas das 3 e 6 horas da manhã foram realizadas no leito com tonômetro de Perkins com o paciente em posição supina (deitado). Imediatamente após a medida no leito deitado, foi realizada outra medida das 6 horas com o paciente sentado. Para realização do TSH, os pacientes ingeriam 1 litro de água, em até 5 minutos. A PIO foi avaliada imediatamente antes e durante uma hora após a ingestão de água, com intervalos de 15 minutos entre as medidas. O TSH foi realizado logo após a avaliação da PIO às 6h da manhã. Foram calculados valores de média (M) e desvio padrão (s) para pico e flutuação e mediana (Md) e quartís (Q2) para flutuação em porcentagem (%). Para comparação de médias foi realizado o teste t de Student para amostras dependentes. Foi utilizado teste de Wilcoxon para comparação de medianas entre amostras dependentes. Para todas as análises foi considerado nível de significância p <0,05. A média dos valores de pico de PIO foi significativamente maior na CTD (20,39 ±1,03 mmHg) do que no TSH (17,37 ± 0,78 mmHg), p < 0,001. A média dos valores de flutuação também foi maior na CTD (10,17 ± 0,90) do que no TSH (5,0 ± 0,45), p < 0,001... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Comparing peak and fluctuation of intraocular pressure (IOP) between diurnal tension curve and water drinking test, detect the peak of IOP, compare the IOP at 6AM in supine and sitting position. 30 right eyes of 30 glaucoma patients with open angle glaucoma (OAG) or ocular hypertension (HO) were submitted to water drinking test (WDT) and diurnal tension curve (DTC). Were evaluated: peak (higher value of IOP observed during WDT and DTC), fluctuation (difference between highest and lowest value of IOP WDT and DTC). IOP was measured with applanation Goldmann tonometry at 9AM, 12AM, 3PM, 6PM, 9PM, 12PM and 6 AM, with the patient sitting. Measurements of 3AM and 6AM were made in bed with Perkins tonometer with the patient in the supine position. Immediately after the measure in supine position, another measure was done at 6AM, with the patient seated. The WDT involved ingestion of 1 liter of tap water in 5 minutes. IOP was measured immediately before and one hour after ingestion of water at intervals of 15 minutes between measurements. The WDT was performed immediately after the measure IOP at 6 AM. For comparison of means was performed Student's t test for dependent samples. Wilcoxon test was used to compare medians between dependent samples. The level of significance was considered p <0.05. The mean peak IOP was significantly higher in the DTC (20.39 ± 1.03 mmHg) than in TSH (17.37 ± 0.78 mmHg), p <0.001. The mean fluctuation was also higher in the DTC (10.17 ± 0.90) than in WDT (5.0 ± 0.45), p <0.001. The value of the fluctuation in the DTC percentile was 90.46% (70.00, 129.90) while the WDT was 35.42% (27.92, 56.95), p <0.001. The IOP of 6 AM showed a statistically significant when performed with the patient in supine position (17,47 mmHg) and sitting (14,30 mmHg) and was significantly higher with the patient in supine position. (p < 0,001). The WDT peak and underestimates of ... (Complete abstract click electronic access below) / Orientador: César Tadeu Spadella / Coorientador: Maria Rosa Bet de Moraes Silva / Banca: Maria de Lourdes Veronese Rodrigues / Banca: Roberto Murad Vessani / Mestre
126

Análise da reprodutibilidade da espessura da camada de fibras nervosas da retina utilizando-se o Spectralis SLO OCT e sua concordância com Stratus OCT

Toscano, Daniela Araújo 10 February 2012 (has links)
Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, 2012. / Submitted by Jaqueline Ferreira de Souza (jaquefs.braz@gmail.com) on 2012-06-27T13:19:21Z No. of bitstreams: 1 2012_DanielaAraujoToscano.pdf: 1639141 bytes, checksum: 9269a3edec99fb2ad296cfabf7f193e7 (MD5) / Approved for entry into archive by Jaqueline Ferreira de Souza(jaquefs.braz@gmail.com) on 2012-06-27T13:19:30Z (GMT) No. of bitstreams: 1 2012_DanielaAraujoToscano.pdf: 1639141 bytes, checksum: 9269a3edec99fb2ad296cfabf7f193e7 (MD5) / Made available in DSpace on 2012-06-27T13:19:30Z (GMT). No. of bitstreams: 1 2012_DanielaAraujoToscano.pdf: 1639141 bytes, checksum: 9269a3edec99fb2ad296cfabf7f193e7 (MD5) / Este estudo teve por objetivo analisar a reprodutibilidade do SD SLO OCT Spectralis e comparar os dados deste OCT com outro já bastante difundido no mercado, como o TDOCT Stratus. Esse estudo foi dividido em duas partes: na primeira delas foram estudados 151 olhos de 79 pacientes sem glaucoma (grupo 1) e 72 pacientes com glaucoma (grupo 2). Para a segunda parte, foram incluídos 110 olhos, sendo 60 sem glaucoma e 50 com glaucoma. Foram realizados em todos os olhos e em apenas uma visita, três B-scans circulares centrados no disco óptico utilizando-se o Spectralis, e na segunda fase, também o Stratus. A média da idade foi de 58 ±11 e 68±10 anos, para o grupo 1 e 2, respectivamente. O ICC, COV e TRV para a média de espessura da camada de fibras nervosas da retina (CFNR) foram respectivamente: 0,94, 2,56% e 4,85m para o grupo 1, e 0,93, 4,65% e 6,61m para o grupo 2. As medidas de espessuras da CFNR foram semelhantes comparando-se os dois aparelhos, com exceção do quadrante superior no grupo 1, e do temporal, no grupo 2 (p<0,0001). Analisando o gráfico de Bland-Altman, foi observado um boa concordância entre as medidas de espessura da CFNR entre o Spectralis e o Stratus. Concluiu-se que o Spectralis apresentou uma excelente reprodutibilidade da espessura da CFNR. Além disso, não houve diferença estatisticamente significante entre as espessuras aferidas com o Spectralis versus o Stratus, exceto no quadrante superior para pacientes sem glaucoma e quadrante temporal para pacientes com glaucoma. Houve uma excelente concordância entre os dois OCTs. _________________________________________________________________________________ ABSTRACT / The goal of the present study was to analyze the reproducibility of SD SLO OCT Spectralis and compare this data with other OCT used worldwide, as TDOCT Stratus. This study was divided in two parts: in the first part a total of 151 eyes of 79 patients without glaucoma (group 1) and 72 glaucomatous patients (group 2) were analyzed. For the second part, 110 eyes, 60 without glaucoma and 50 with glaucoma were enrolled. All patients’ eyes were scanned using the Spectralis and in the second part of the study, also the Stratus. Three consecutive circular B-scan centered at the optic disc were performed in one visit. The average age was 58±11 and 68±10 years old for the group 1 and 2, respectively. The ICC, COV and TRV for the mean RNFL thickness were respectively: 0.94, 2.56% and 4.85m for the group 1, and 0.93, 4.65% and 6.61m for the group 2. Only in the superior quadrant for the group 1 and temporal for the group 2, the RNFL thickness difference was statistically significant (p0.0001). Analyzing the Bland-Altman concordance graphs it was observed excellent concordance between the RNFL thickness measured by Spectralis and Stratus. The Spectralis showed excellent reproducibility with regard to RNFL thickness measurements. In addition, there were no statistically significant differences between RNFL measurements by Spectralis and Stratus, except for superior quadrant in the patients without glaucoma and temporal quadrants in glaucomatous patients. In conclusion, there was an excellent concordance between the two OCTs.
127

Efeito da redução da pressão intraocular sobre a camada de fibras nervosas retinianas e nervo óptico medido pela tomografia de coerência óptica

Araújo, Candice Cristina Quirino de 05 April 2013 (has links)
Dissertação (mestrado)—Universidade de Brasília, Programa de Pós-Graduação em Ciências da Saúde, 2013. / Submitted by Albânia Cézar de Melo (albania@bce.unb.br) on 2013-05-21T15:56:58Z No. of bitstreams: 1 2013_CandiceCristinaQuirinoAraujo.pdf: 1613577 bytes, checksum: 034c8c8d4b10aa239213238a797195cb (MD5) / Approved for entry into archive by Guimaraes Jacqueline(jacqueline.guimaraes@bce.unb.br) on 2013-05-21T16:03:51Z (GMT) No. of bitstreams: 1 2013_CandiceCristinaQuirinoAraujo.pdf: 1613577 bytes, checksum: 034c8c8d4b10aa239213238a797195cb (MD5) / Made available in DSpace on 2013-05-21T16:03:51Z (GMT). No. of bitstreams: 1 2013_CandiceCristinaQuirinoAraujo.pdf: 1613577 bytes, checksum: 034c8c8d4b10aa239213238a797195cb (MD5) / Introdução: Glaucoma é uma neuropatia óptica progressiva, multifatorial, associada à perda de campo visual e às alterações no nervo óptico (NO) e camada de fibras nervosas retinianas (CFNR). Objetivo: Identificar alterações na CFNR e no NO, por meio da tomografia de coerência óptica (OCT), em pacientes com glaucoma primário de ângulo aberto (GPAA), submetidos a tratamento clínico e cirúrgico (trabeculectomia). Métodos: Foi realizada análise prospectiva de 37 olhos de 25 pacientes avaliados antes e após os tratamentos por meio da OCT, num período pré-tratamento (1 semana a 1 mês) e com 1, 3 e 6 meses após o tratamento. Os parâmetros medidos pela OCT foram analisados pelo teste de igualdade de médias e, para correlação entre as variáveis e a Po (pressão intraocular), foi utilizado o método de Pearson. Resultados: Os pacientes apresentaram redução da Po acima de 30%. O grupo clínico apresentou aumento da espessura média da CFNR total (p=0,009) e inferior (p = 0,007). Houve aumento da espessura média da CFNR superior, temporal e nasal, aumento da área de rima e diminuição do volume de escavação, entretanto sem significância estatística. O grupo cirúrgico apresentou aumento da espessura média da CFRN inferior e redução do volume de escavação quando correlacionados com a Po (p=0,004 / p= 0,02). Houve aumento da CFRN temporal, diminuição da área de escavação e aumento da área de rima, entretanto sem significância estatística. Conclusão: O grupo clínico apresentou aumento significante na espessura da CFNR. O grupo cirúrgico apresentou diminuição do volume de escavação e aumento da espessura da CFRN dependentes da redução da Po. ______________________________________________________________________________ ABSTRACT / Introduction: Glaucoma is a progressive optic neuropathy, multifactorial, associated with visual field loss and changes in the optic nerve (ON) and retinal nerve fiber layer (RNFL). Objective: To identify changes in the RNFL and ON by optical coherence tomography (OCT) in patients with primary open angle glaucoma (POAG)undergoing clinical and surgical treatment (trabeculectomy). Methods: We performed a prospective analysis of 37 eyes of 25 patients before and after treatment, by means of OCT, a pre-treatment period (1 week to 1 month) and with 1, 3 and 6 months after treatment. The parameters measured by OCT were analyzed by the test of equality of means and correlations between IOP and variables we used the method of Pearson. Results: The patients showed reduction of IOP above 30%. The clinical group had an increase in average total (p= 0,009) and inferior RNFL thickness (p = 0.007). There was an increase in average superior, temporal and nasal RNFL thickness, increase in rim area and decreased in cup volume, however not statistically significant. The surgical group had an increase in average inferior RNFL thickness and reducing in cup volume when correlated with IOP (p = 0.004 / p = 0.02). There was an increase in temporal RNFL thickness, decrease in cup area and increase in rim area, though not statistically significant. Conclusion: The clinical group showed significant increase in RNFL thickness. The surgical group showed decrease in the cup volume and increased RNFL thickness dependent reduction of IOP.
128

Estudo da eficácia do agulhamento transconjuntival com 5-fluoracil em olhos com pressão intraocular elevada e bolha encapsulada pós trabeculectomia / The efficacy of transconjunctival needling revision with 5- fluorouracil in encapsulated blebs with elevated intraocular pressure after trabeculectomy

Ricardo Suzuki 03 February 2014 (has links)
Objetivo: Estudo comparativo da pressão intraocular (PIO) após agulhamento transconjuntival (ATC) com 5-fluoracil (5-FU) e tratamento clínico (TC) em olhos glaucomatosos com bolha encapsulada e PIO não controlada após trabeculectomia com mitomicina C (MMC), no final de 12 meses de seguimento. Desenho: Estudo prospectivo, randomizado, intervencionista. Participantes: 40 olhos de 39 pacientes com bolha encapsulada, desenvolvida em 5 meses ou menos, após trabeculectomia primária com mitomicina e PIO >= 20mmHg. Métodos: Os olhos foram randomizados para ATC com 5-FU e TC. Um máximo de dois ATC foi permitido no estudo. Todos os olhos foram acompanhados por 12 meses. O sucesso foi definido como PIO <= 18 mmHg e redução de 20% da PIO basal (sem medicações no grupo ATC). Resultados: A média da PIO em 12 meses de acompanhamento foi de 12,14 ± 2,80 mmHg no grupo do ATC e 15,13 ± 2,07 mmHg no grupo do TC (p = 0,004). 14 olhos (70%) foram considerados sucesso no grupo do ATC e 15 olhos (75%) no grupo do TC (p = 0,89). O número médio de agulhamentos foi de 1,35 ± 0,49 e a quantidade média de medicamentos foi de 2,15 ± 0,74. Conclusões: Houve uma taxa de sucesso semelhante nos olhos randomizados para ATC com 5-FU em comparação com TC em 12 meses de seguimento. No entanto, foi observada uma significativa menor média da PIO, após o ATC / Objective: To compare de efficacy of transconjuctival needling revision (TNR) with 5-fluorouracil (5-FU) and medical treatment (MT) in glaucomatous eyes with encapsulated bleb and uncontrolled intraocular pressure (IOP) after trabeculectomy with mitomycin C (MMC) at 12 months follow-up. Design: Prospective, randomized, interventional study. Participants: Forty eyes of 39 patients with encapsulated bleb developed in 5 months or less following primary trabeculectomy with mitomycin and IOP >= 20mmHg. Methods: Eyes were randomized to either TNR with 5-FU or MT. A maximum of two TNR was allowed in the study. All eyes were followed-up for 12 months. Success of treatment was defined as IOP <= 18mmHg and a 20% reduction from baseline (no medications in TNR group). Results: Mean IOP at 12 months follow-up was 12.14 ± 2.80 mmHg in the TNR group and 15.13 ± 2.07 mmHg in the MT group (p=0.004). Fourteen eyes (70%) were considered a success in the TNR group and 15 eyes (75%) in the MT group (p=0.89). The number of needling procedure was 1.35 ± 0.49 procedures and the number of medication was 2.15 ± 0.74 medications. Conclusions: We have demonstrated a similar success rates in eyes randomized to MT in comparison to TNR with 5-FU at the last follow-up. However, a significant lower mean IOP after TNR was observed
129

The Role of SPARC in Aqueous Humor Outflow and TGFß2-mediated Ocular Hypertension in a Murine Model

Swaminathan, Swarup Sai 07 July 2014 (has links)
Glaucoma is the leading cause of irreversible blindness worldwide, and is a major cause of blindness in the United States. It affects approximately 5% of Caucasians and 10% of African- Americans over the age of 60 years. Elevated intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma. Impaired outflow of aqueous humor from the eye is thought to be the cause of pathologically elevated IOP. However, the etiology of outflow impairment is unknown. Anatomically, the aqueous humor drains into the iridocorneal angle of the eye, where the iris inserts at the transition between the cornea and sclera. In humans, approximately 80-90% of the aqueous traverses through the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), Schlemm’s canal, collector channels and empties into episcleral veins. Abnormalities at these sites are thought to cause impaired outflow. Abnormal accumulation of extracellular matrix (ECM) in the TM or JCT, abnormal endothelial function in Schlemm’s canal, or a combination of these components have been strongly implicated. Our laboratory has focused on the role of Secreted Protein Acidic and Rich in Cysteine (SPARC) in regulating outflow. SPARC is the prototypical matricellular protein that mediates ECM organization and turnover in numerous human tissues. Our lab was first to demonstrate that SPARC is highly expressed in the TM and JCT regions of the eye, and that the SPARC knockout (KO) mouse has a significant decrease in IOP of 15-20%. SPARC may affect the degree of segmental flow, a theory that states that variable aqueous outflow occurs around the circumference of the eye; only certain portions of the TM are thought to display active outflow at any particular moment. The cytokine transforming growth factor-ß2 (TGFß2) has been shown to modulate multiple ECM proteins, including SPARC. TGFß2 is significantly upregulated by 2 to 3-fold in the aqueous humor of glaucoma patients compared to controls. In addition, when TGFß2 is overexpressed in rodent eyes, increased ECM deposition is observed within the trabecular meshwork leading to IOP elevation. SPARC is one of the most highly upregulated proteins by TGFß2, and is downstream of TGFß2. We hypothesized that wild-type (WT) mice would demonstrate segmental flow, while SPARC KO mice would display a more continuous pattern of outflow around the eye. We also believed that IOP would be inversely correlated with outflow area. We also hypothesized that SPARC is essential to the process of TGFß2-mediated ocular hypertension, and that the lack of SPARC would impair IOP elevation. We conducted a tracer study utilizing fluorescent microbeads to determine the location of outflow circumferentially around the mouse TM. Microbeads were injected intracamerally into the eyes of WT and KO mice. After a 45-minute incubation period, the mice were euthanized and eyes were processed for confocal, light, and electron microscopy. During the second group of experiments, empty or TGFß2-containing adenovirus was injected intravitreally into WT and SPARC KO mice and IOP was measured for 2 weeks. Immunohistochemistry was completed on all tissues to assess for changes in major ECM proteins. Percentage effective filtration length (PEFL), or area of the TM labeled by tracer, was significantly increased in SPARC KO mice (70.61% ± 11.36%, p<0.005; N=11) compared to WT mice (54.68% ± 9.95%; N=11). In addition, the pressures between the two sets of eyes were significantly different with mean pressures of 16.3 mm Hg in WT mice and 12.6 mm Hg in KO mice (p<0.005, N=11 pairs). In addition, PEFL and IOP were inversely correlated with R2 = 0.72 (N=10 pairs); in eyes with higher IOP, PEFL was reduced. Electron microscopy demonstrated that high-tracer TM areas had a greater separation between trabecular beams. Collagen fibril diameter was found to be smaller in the KO (28.272 nm) compared to WT (34.961 nm; p<0.0005, N=3 pairs). These data provided structural correlations to the functional data regarding segmental flow. In the second set of experiments, IOP was found to be significantly elevated in TGFß2- injected WT mice compared to empty vector-injected WT mice during days 4-11 (p<0.05, N=8). However, IOP was not significantly elevated in TGFß2-injected KO mice compared to controls. Immunohistochemistry demonstrated that TGFß2 increased expression of collagen IV, fibronectin, plasminogen activator inhibitor-1 (PAI-1), connective tissue growth factor (CTGF), and SPARC within the TM of WT mice, but only PAI-1 and CTGF in KO mice (p<0.05, N=3 pairs). These data support our hypotheses, indicating that SPARC plays an integral role in the modulation of aqueous humor outflow. In addition, it appears as though SPARC is essential to the regulation of TGFß2-mediated ocular hypertension. Aside from providing further evidence of the importance of ECM in IOP regulation, our work presents the novel discovery of segmental flow in the mouse. Given the potential role of SPARC in TGFß2-mediated ocular hypertension, SPARC may not only play an integral role in ECM homeostasis within the trabecular meshwork, but may be a valuable target for pharmacologic therapy in treating primary open-angle glaucoma.
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Avaliação da frequencia e do tipo de mutações no gene TIGR/MYOC em uma população brasileira com glaucoma primario de angulo aberto do tipo juvenil

Vasconcellos, Jose Paulo Cabral de 31 July 2018 (has links)
Orientador: Vital Paulino Costa / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-07-31T16:59:35Z (GMT). No. of bitstreams: 1 Vasconcellos_JosePauloCabralde_D.pdf: 988691 bytes, checksum: ed9aef7fcff38c1838bfc4261d1754b0 (MD5) Previous issue date: 2001 / Doutorado

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