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Epithelial wound healing is a common occurrence in many organisms. In spite of a long history of study in this field, we do not have a complete understanding of the molecular and cellular mechanisms of wound healing, which is a key element to appreciate in order to modulate this process for better clinical outcomes. Optimal outcomes are especially critical in the cornea as a failure to regenerate can result in blindness and a huge decline in quality of life. Matrix Metalloproteinases (MMPs) are a family of zinc dependent proteases that have been shown to be both regulators and effectors of the corneal wound healing process. Strict regulation of MMP-9, the most extensively studied member of the MMP family, has been shown to be critical for efficient wound regeneration. While we now know that MMP-9 is important, and we even have evidence defining some of the roles it plays in the corneal wound healing process, the mechanism by which MMP-9 is regulated is still under debate. Possible extracellular regulatory mechanisms range from cell-cell interactions to cell-matrix interactions to secreted factors. However, the detailed mechanism of events that takes place on the extracellular surface and the downstream signals that mediate MMP-9 are unknown. Therefore, one of the objectives of the presented work is to define the external mechanisms which mediate MMP-9 expression in resurfacing epithelial cells and to link these external signals to internal signaling pathways in vitro. Furthermore, while MMP-9 acts to slow the resurfacing phase of wound healing, other MMPs seem to cause opposing effects. The second objective of the presented work is to provide the first global spatial and temporal MMP expression profile for an in vivo epithelial wound healing scenario and to define possible macroscopic roles of these heretofore unknown MMPs. Finally, this thesis will look at the expression of many MMP family members in a penetrating model which is an increasingly more common wound scenario due to the increase in corrective surgery. The final objective is to examine human post-LASIK corneas and correlate MMP expression with age, post-operative time, or histopathological abnormalities. The knowledge obtained from all aspects of these studies will contribute to the current understanding and knowledge about the roles and regulatory mechanisms of MMPs in the corneal wound healing process.

Ο σκοπός της εργασίας αυτής είναι ο προσδιορισμός της ακρίβειας του πάχους του flap που δημιουργείται από τον μικροκερατόμο Moria M2 και του πάχους του κερατοειδή μετεγχειρητικά με την χρήση του σαρωτή υπερήχων υψηλής συχνότητας (η μεγαλύτερης ακρίβειας μέθοδος) και του Orbscan (η πιο δημοφιλής μέθοδος μέτρησης). / The purpose of this study is to evaluate the precision of the flap thickness of Moria M2 Microkeratome by using Artemis Very High Frequency Ultrasound Scanning and the evaluation of the postoperative corneal thickness with Orbscan and Artemis

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains x, 100 p.; also includes graphics. Includes bibliographical references (p. 91-100).

Connexin 43 (Cx43) is a gap junction protein that enables direct cell-to-cell communication in many tissues of the body and stressful environments such as injury and hypoxia affect its expression. In addition to affecting Cx43 expression, hypoxia also retards wound-healing rates. Using rat corneal organ cultures, this thesis aims to define hypoxia's role in the expression and localization of Cx43 in wounded corneas. Tissue samples were stained immunohistochemically at three different time points after injury, 2.5 hours, 5 hours, and 18 hours. It was determined that under hypoxic conditions, Cx43 is more highly expressed than under normoxic conditions after injury. While Cx43 expression follows the same spatial pattern throughout the healing process in the cornea under both normoxic and hypoxic conditions, the pattern is delayed under hypoxic conditions. These results provide a possible reason why wound closure is delayed in low oxygen environments.

Made available in DSpace on 2014-06-11T19:23:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-06-05Bitstream added on 2014-06-13T20:30:41Z : No. of bitstreams: 1 donatti_c_me_botfmvz.pdf: 2093911 bytes, checksum: d264970227347791e8738946cc4ac63c (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A córnea é a estrutura anterior transparente do olho e apresenta-se muito susceptível a traumas e agressões. O objetivo do presente estudo foi avaliar e comparar, clínica e histomorfometricamente, o processo de reparação corneana de úlceras induzidas em coelhos, frente à utilização do plasma rico em plaquetas (PRP) sob a forma de colírio ou tampão. Foram utilizadas 60 fêmeas da espécie leporina, constituindo-se 4 grupos experimentais de 15 animais cada, designados grupo plaquetas (GP), grupo tampão (GT), grupo controle (GC) e grupo controle amniótica (GA). Em todos os animais foi realizada a úlcera experimental, sendo este o único procedimento no GC. No GP, os coelhos foram medicados com colírio autólogo de plasma rico em plaquetas. No GC, foi instilado colírio lubrificante. No GT, foi aplicado tampão sólido rico em plaquetas, revestido por membrana amniótica, para a retenção do mesmo. No GA, foi aplicada apenas a membrana amniótica. Os grupos experimentais foram subdivididos em três subgrupos (M4, M7, M30), de acordo com os períodos finais de avaliação. Os animais foram avaliados por meio de exame clínico e histomorfométrico. Não houve diferenças entre os tratamentos utilizados quanto aos sinais relacionados à sensibilidade ocular, quemose e secreção ocular. Os grupos tratados com PRP, na forma de tampão ou colírio, apresentaram menor opacidade do que os animais tratados apenas com membrana amniótica no momento final de avaliação. Quanto à presença da úlcera corneana, os grupos tratados com PRP (GP e GT) apresentaram menor intensidade de ulceração corneana com relação aos demais grupos (GC e GA). Na avaliação histológica verificou-se maior epitelização corneana na fase inicial da lesão no tratamento à base de colírio de PRP. O uso da membrana amniótica promoveu espessamento do epitélio e estroma corneano, com sinergismo da mesma quando associada ao PRP / The cornea is the transparent anterior part of the eye and is very susceptible to trauma and sore. The aim of this work was to evaluate and compare both, clinically and histomorphometrically the process of repair of induced corneal ulcer in rabbits using platelet-rich plasma in the form of eyedrop or clot. Sixty female leporids were divided into four groups of 15 animals, and named as platelet group (PG), clot group (CLG), control group (CG), and amniotic control group (AG). Ocular ulcer was experimentally induced in all the animals. Ulcer induction was the single procedure performed in CG. In PG, autologous platelet-rich plasma as a eyedrop was used five times a day for seven days. In CLG, a platelet-rich clot was covered by amniotic membrane to hold it in place was used. In AG, only the amniotic membrane was used. Experimental groups were then subdivided into three groups (M4, M7, M30), corresponding to the end of the evaluation period. The animals were evaluated through clinical and histomorphometric tests. There were no differences between treatments related to ocular sensitivity (blepharospasm and photophobia), chemosis and ocular secretion. The groups treated with PRP either as eyedrop or a clot, showed less opacity than the animals treated only with amniotic membrane at the moment of the final evaluation. The presence of corneal ulcers in the groups treated with PRP (PG and CLG) showed lower intensity than the other groups (CG and AG). In histological evaluation, corneal epithelization at the initial phase of the lesion was confirmed when using PRP. The use of amniotic membrane promoted corneal epithelial and stromal thickness, as well as synergism when associated to PRP

nÃo hà / Com a cirurgia de catarata moderna realizada em cÃrneas normais, independente da tÃcnica cirÃrgica utilizada, hà uma perda celular endotelial mÃdia de 10 a 20%. SubstÃncias viscoelÃsticas foram desenvolvidas com a funÃÃo de manter os espaÃos naturais do olho e conferir proteÃÃo mecÃnica Ãs estruturas intraoculares durante a cirurgia. O objetivo deste estudo foi realizar uma anÃlise comparativa do efeito de duas formulaÃÃes viscoelÃsticas, metilcelulose a 2% e 4%, na proteÃÃo do endotÃlio corneano contra o dano secundÃrio à facoemulsificaÃÃo. Foi realizado um estudo prospectivo, randomizado e duplo cego com pacientes portadores de catarata senil, submetidos à cirurgia de facoemulsificaÃÃo com Implante de Lente Intraocular (LIO). Todos os pacientes foram submetidos a uma avaliaÃÃo oftalmolÃgica completa, incluindo microscopia especular. ApÃs o exame inicial, os pacientes foram randomizados em dois grupos: no grupo A (n=63) foi utilizada a metilcelulose 2% e no grupo B (n=63) a metilcelulose 4%. A mÃdia da Densidade de CÃlulas Endoteliais (DCE) mostrou-se significativamente reduzida (p<0,05), tanto na anÃlise intra como na intergrupo no 1Â, 15 e 30 dias de pÃs-operatÃrio, representando uma perda de cÃlulas endoteliais de 15,26% e 6,79% nos grupos A e B, respectivamente. A Espessura Central da CÃrnea (ECC) mostrou-se aumentada no 1 dia pÃs operatÃrio (DPO) no grupo A, sendo este dado estatisticamente significante (p<0,05). Houve aumento no Coeficiente de VariaÃÃo da tamanho celular (CV) e diminuiÃÃo no Percentual de CÃlulas Hexagonais (6 A), no entanto, sem significÃncia estatÃstica para esses dois parÃmetros. ConcluÃmos que, à despeito das vantagens da metilcelulose a 4% em relaÃÃo à diminuiÃÃo de perdas de cÃlulas endoteliais apÃs facoemulsificaÃÃo, ambos os viscoelÃsticos sÃo semelhantes em relaÃÃo a parÃmetros clÃnicos como ECC, CV e 6A, os quais refletem a manutenÃÃo de condiÃÃes fisiologicamente adequadas para o bom funcionamento do endotÃlio. No entanto, devido à pequena diferenÃa de custo entre os dois produtos e os benefÃcios da metilcelulose 4%, esta pode ser considerada um produto de escolha em cirurgias de catarata de rotina, uma vez que as indicaÃÃes de facoemulsificaÃÃo estÃo sendo cada vez mais precoces, devido Ãs exigÃncias visuais dos pacientes, promovendo, desta forma, cÃrneas mais saudÃveis por longo prazo. / Modern cataract surgery in normal corneas, independent of the surgical technique used, causes a mean 10 to 20% loss of endothelial cells. Viscoelastic substances were developed with the function of maintaining the natural spaces of the eye and providing mechanical protection to the intraocular structures during surgery. The objective of this study was to perform a comparative analysis of the effect of two viscoelastic compositions, methylcellulose 2% and 4%, in corneal endothelial protection against secondary damage to the phacoemulsification procedure. We performed a prospective, randomized, double-blind study with senile cataract patients, submitted to phacoemulsification surgery with intraocular lens (IOL) implant. All patients were submitted to a complete ophthalmological assessment, including specular microscopy. After initial assessment, the patients were randomized into two groups: in Group A (n=63) we used methylcellulose 2%, and in Group B (n=63) methylcellulose 4%. There was no statistically significant difference for the parameters analyzed between groups before surgery. However, at 30 days after surgery, mean density of endothelial cells (DCE) was 2128.78Â277.55 cells/mm in Group A and 2395.79Â262.16 cells/mm in Group B, representing a 15.15 and 6.76% loss of endothelial cells in Groups A and B, respectively. Mean DCE was significantly reduced (p<0.05), in both the inter- and inter-group analysis on the 1st, 15th, and 30th day after surgery. ECC increased on the 1st day after surgery in group A, this datum was statistically significant (p<0.05). There was no statistical difference for the other parameters assessed. In this study, we conclude that, despite the advantages of methylcellulose 4% over 2% in regards to the reduction of endothelial cell loss after phacoemulsification, both viscoelastic substances are similar in relation to clinical parameters such as central corneal thickness, coefficient of variation in cell size and percentage of hexagonal cells, which reflect corneal preservation and maintain adequate physiological conditions for proper endothelial function. However, due to the slight difference in cost between the two products and the benefits of methylcellulose 4% on endothelial cell preservation, this may be considered a choice product in routine cataract surgery, as indications for phacoemulsification are increasingly early, due to patientsâ visual demands, promoting, in this manner, healthier corneas in the long term.

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Orientador: Newton Kara-Jose / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T21:13:45Z (GMT). No. of bitstreams: 1 Santos_MarcioAlexandreAraujoFlorenciodos_D.pdf: 1714788 bytes, checksum: 4df269b178244131a0b3d831ea27e272 (MD5) Previous issue date: 2009 / Resumo: Os objetivos deste estudo foram identificar o perfil epidemiológico dos familiares responsáveis pela autorização ou recusa à doação de córneas de seus parentes falecidos no Hospital de Clínicas da Universidade Estadual de Campinas; suas razões para autorizar ou não a doação; e razões para ser ou não doador de córneas. O estudo foi desenvolvido na Faculdade de Ciências Médicas, no Hospital de Clínicas da Universidade Estadual de Campinas - Unicamp, Campinas, São Paulo, Brasil, entre dezembro de 2005 e dezembro de 2006. O desenho adotado nesta pesquisa foi um estudo transversal do tipo analítico e descritivo, realizado através de questionário testado em estudo piloto. A amostra populacional desse estudo foi calculada baseado em teste estatístico para estudo descritivo e variável qualitativa. Foram realizadas 184 entrevistas e os resultados sugeriram que os familiares que eram solteiros, divorciados ou separados; católicos ou sem religião; que possuíam conhecimento que sua religião era a favor da doação; que possuíam atitudes altruísticas; que possuíam algum grau de conhecimento sobre doação e que obtinham informação sobre doação pela TV ou rádio, autorizaram mais a doação das córneas de seu parente falecido. As razões citadas para autorizar a doação de córneas foram: solidariedade às famílias que esperam por uma córnea; respeito ao desejo em doar do falecido; atitude altruística de ajudar ao próximo; conforto ao momento de dor que a família vivia. E as razões citadas contra a doação foram: respeito ao desejo em não doar do parente falecido; desconfiança na utilização da córnea; demora para captar a córnea e razões religiosas. O conhecimento desse perfil e dessas razões poderá levar a um melhor entendimento da recusa familiar e assim, planejar medidas mais efetivas para aumentar a doação de córneas. / Abstract: The objectives of this study was to identify the epidemiological profile of the family responsible for granting or refusing the donation of corneas of their deceased relatives in the Clinical Hospital of State University of Campinas and identify their reasons for granting or not giving, and reasons to be or not donor corneas. The study was conducted at the College of medical Sciences of Clinical Hospital of state University of Campinas, São Paulo, Brazil, between December 2005 and December 2006. The design adopted in this research study was a cross-sectional analytical and descriptive study through a questionnaire tested in a pilot study. The sample population of this study was calculated based on statistical test for a descriptive and qualitative variable. One hundred eighty four interviews were conducted and the results suggested that family members who were single, divorced or separated, Catholic or no religion, who had knowledge that their religion was in a favor donation, which had altruistic attitudes, which had some degree of knowledge about cornea donation and they obtained information about donation by TV or radio were more significant to authorize the donation of corneas of their deceased relative. Reasons cited to authorize the donation of corneas were: solidarity, the deceased wanted to donate, altruistic attitude to the next, comfort the moment of pain that the family lived. And the reasons cited against the donation were the deceased relative did not want to be a donor, do not have confidence in the use of the cornea, the delay to capture the cornea and religion reasons. Knowledge of this profile and theses reasons may lead to a better understanding of family refusal and so, plan the most effective measures to increase the donation of corneas. / Doutorado / Oftalmologia / Doutor em Ciências Médicas