Ação de prostaglandinas tópicas na conjuntiva de coelhos.
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Data
2019-02-26
Autores
Aguiar, Evian Valli
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Universidade Estadual Paulista (Unesp)
Resumo
A utilização prolongada de colírios análogos de prostaglandinas (AP) no tratamento do glaucoma tem sido associada a alterações tóxicas e inflamatórias dos tecidos oculares. As causas destes efeitos adversos locais ainda não são bem conhecidas. Uma das hipóteses aventadas seria o efeito citotóxico dos conservantes dos colírios e outra o envolvimento das metaloproteinases, cuja expressão estaria relacionada às alterações estruturais induzidas pelo uso crônico dos AP. Objetivo: O objetivo deste estudo foi avaliar a conjuntiva de coelhos submetidos à tratamento ocular tópico com AP e solução conservante por meio de estudo histológico, morfométrico e imuno-histoquímico. Material e Métodos: Quarenta coelhos adultos sadios da raça Norfolk, de ambos os sexos, com peso entre 1500 e 2500g, foram divididos por sorteio em quatro grupos experimentais. Os olhos direitos dos animais foram tratados com uma gota diária de bimatoprosta 0,03%, travoprosta 0,004%, latanoprosta 0,005%, e solução conservante por 30 dias (20 animais) e 60 dias (20 animais). Todos os coelhos foram submetidos à avaliação clínica oftalmológica com documentação fotográfica. Após a eutanásia, os olhos foram enucleados e preparados para análise histológica, morfométrica e imuno-histoquímica com pesquisa de expressão de metaloproteinase 2 (MMP2). Resultados: Houve aumento de espessura epitelial e estromal em todos os grupos tratados, principalmente no grupo latanoprosta com 30 dias e bimatoprosta com 60 dias (p<0,001). A análise histológica com 30 dias revelou infiltração linfocitária, degeneração vacuolar, perda da relação núcleo citoplasma, corpos apoptóticos, diminuição das células caliciformes, principalmente nos grupos bimatoprosta e travaprosta. Com 60 dias houve intensa desorganização tecidual em todos os grupos tratados, com metaplasia escamosa no grupo latanoprosta. No grupo conservante as alterações morfológicas foram leves com 30 dias e se intensificaram com 60 dias, apresentando hiperplasia do epitélio e anaplasia. A expressão da MMP2 foi mais pronunciada nos grupos tratados com AP nos primeiros 30 dias. Conclusão: Todas as medicações testadas, inclusive a solução conservante, causaram algum grau de inflamação e deterioração tecidual na conjuntiva depois de 30 ou 60 dias de tratamento. Houve expressão da MMP2, mais acentuada na fase aguda do experimento.
Prolonged use of prostaglandin (PA) analog drops in the treatment of glaucoma has been associated with toxic and inflammatory changes in ocular tissues. The causes of these local adverse effects are not yet well known. One of the hypotheses proposed would be the cytotoxic effect of the preservatives of the eye drops and another the involvement of the metalloproteinases, whose expression would be related to the structural alterations induced by the chronic use of PA. Objective: The objective of this study was to evaluate the conjunctiva of rabbits submitted to topical ocular treatment with PA and preservative solution by histological, morphometric and immunohistochemical study. Material and Methods: Forty healthy adult Norfolk rabbits, weighing between 1500 and 2500g, were divided by lot into four experimental groups. The right eyes of animals were treated with a daily drop of 0.03% bimatoprost, 0.04% travoprost, 0.005% latanoprost, and placebo preservative solution for 30 days (20 animals) and 60 days (20 animals). All rabbits were submitted to clinical ophthalmological evaluation with photographic documentation. After euthanasia, the eyes were enucleated and prepared for histological, morphometric and immunohistochemical analysis with metalloproteinase 2 (MMP2) expression research. Results: There was an increase in epithelial and stromal thickness in all treated groups, mainly in the 30 day latanoprost group and 60 day bimatoprost group (p <0.001). Histological analysis with 30 days revealed lymphocytic infiltration, vacuolar degeneration, loss of nucleus cytoplasm, apoptotic bodies, decrease of goblet cells, especially in the bimatoprost and travaprost groups. At 60 days there was intense tissue disorganization in all treated groups, with squamous metaplasia in the latanoprost group. In the preservative group, the morphological changes were mild at 30 days and intensified at 60 days, presenting epithelial hyperplasia and anaplasia. The expression of MMP2 was more pronounced in PA treated group in the first 30 days. Conclusion: All medications tested, including the preservative solution, caused some degree of inflammation and tissue deterioration in the conjunctiva after 30 or 60 days of treatment. There was MMP2 expression, more pronounced in the acute phase of the experiment.
Prolonged use of prostaglandin (PA) analog drops in the treatment of glaucoma has been associated with toxic and inflammatory changes in ocular tissues. The causes of these local adverse effects are not yet well known. One of the hypotheses proposed would be the cytotoxic effect of the preservatives of the eye drops and another the involvement of the metalloproteinases, whose expression would be related to the structural alterations induced by the chronic use of PA. Objective: The objective of this study was to evaluate the conjunctiva of rabbits submitted to topical ocular treatment with PA and preservative solution by histological, morphometric and immunohistochemical study. Material and Methods: Forty healthy adult Norfolk rabbits, weighing between 1500 and 2500g, were divided by lot into four experimental groups. The right eyes of animals were treated with a daily drop of 0.03% bimatoprost, 0.04% travoprost, 0.005% latanoprost, and placebo preservative solution for 30 days (20 animals) and 60 days (20 animals). All rabbits were submitted to clinical ophthalmological evaluation with photographic documentation. After euthanasia, the eyes were enucleated and prepared for histological, morphometric and immunohistochemical analysis with metalloproteinase 2 (MMP2) expression research. Results: There was an increase in epithelial and stromal thickness in all treated groups, mainly in the 30 day latanoprost group and 60 day bimatoprost group (p <0.001). Histological analysis with 30 days revealed lymphocytic infiltration, vacuolar degeneration, loss of nucleus cytoplasm, apoptotic bodies, decrease of goblet cells, especially in the bimatoprost and travaprost groups. At 60 days there was intense tissue disorganization in all treated groups, with squamous metaplasia in the latanoprost group. In the preservative group, the morphological changes were mild at 30 days and intensified at 60 days, presenting epithelial hyperplasia and anaplasia. The expression of MMP2 was more pronounced in PA treated group in the first 30 days. Conclusion: All medications tested, including the preservative solution, caused some degree of inflammation and tissue deterioration in the conjunctiva after 30 or 60 days of treatment. There was MMP2 expression, more pronounced in the acute phase of the experiment.
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conjuntiva, coelhos, inflamação, análogos de prostaglandinas, metaloproteinase 2, imuno-histoquímica, conjunctiva, rabbits, inflammation, prostaglandin analogs, metalloproteinase 2, immunohistochemistry