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J Cell Mol Med ; 24(9): 5195-5204, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32267082

RESUMO

Prostaglandin analogues (PG), beta-blockers (BB) or their combination (PG+BB) are used primarily to reduce the intraocular pressure (IOP) pathologically associated with glaucoma. Since, fibrosis of the trabecular meshwork (TM) is a major aetiological factor in glaucoma, we studied the effect of these drugs on fibrosis-associated gene expression in TM of primary glaucoma patients. In the present study, TM and iris of primary open-angle (n = 32) and angle-closure (n = 37) glaucoma patients were obtained surgically during trabeculectomy and categorized based on the type of IOP-lowering medications use as PG, BB or PG+BB. mRNA expression of pro-fibrotic and anti-fibrotic genes was quantified using qPCR in these tissues. The gene expression levels of pro-fibrotic genes were significantly lower in PG+BB as compared to other groups. These observations and underlying signalling validated in vitro in human TM cells also showed reduced fibrotic gene and protein expression levels following PG+BB treatment. In conclusion, it is observed that PG+BB combination rather than their lone use renders a reduced fibrotic status in TM. This further suggests that IOP-lowering medications, in combination, would also modulate fibrosis-associated molecular changes in the TM, which may be beneficial for maintaining aqueous out-flow mechanisms over the clinical treatment duration.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Regulação da Expressão Gênica , Glaucoma/tratamento farmacológico , Glaucoma/genética , Prostaglandinas/agonistas , Malha Trabecular/metabolismo , Antagonistas Adrenérgicos beta/farmacologia , Estudos de Coortes , Quimioterapia Combinada , Feminino , Fibrose , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Prostaglandinas Sintéticas/farmacologia , Prostaglandinas Sintéticas/uso terapêutico , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/patologia
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