Scholarlink

<p>Glaucoma remains the leading cause of irreversible blindness worldwide, with elevated intraocular pressure (IOP) being the only modifiable risk factor in primary open-angle glaucoma (POAG). Despite adequate IOP control, many patients continue to progress to irreversible optic neuropathy, emphasising the need for alternate treatments. Transforming growth factor-beta (TGF-β) promotes extracellular matrix (ECM) production and fibrosis at the optic nerve head (ONH) in glaucoma. A disintegrin and metalloprotease-12 and metalloprotease-19 (ADAM12 and ADAM19) are implicated in fibrosis. Recent studies have explored miRNA-based manipulation of the TGF-β signalling pathway as a potential therapeutic strategy in fibrosis. This study investigates whether miR-29b modulation affects ADAM12, ADAM19, and ECM gene expression in human lamina cribrosa (LC) cells. Primary human normal lamina cribrosa (NLC) and glaucoma LC (GLC) cells were treated with TGF-β1 and transfected with either a miR-29b mimic or control. Gene expression levels of ADAM12, ADAM19, miR-29b, and several ECM genes were quantified using real-time RT-qPCR, and protein expression levels by Western blotting. ADAM12 and ADAM19 expression was elevated in untreated GLC cells, and treatment with TGF-β1 in both NLC and GLC cells increased ADAM12 and ADAM19 expression. The expression of miR-29b was significantly reduced in both GLC- and TGF-β1-treated NLC and GLC cells. Transfection with miR-29b resulted in a marked reduction in ADAM12 and ADAM19 mRNA expression in TGF-β1-treated NLC and GLC cells. Additionally, miR-29b transfection reduced ECM gene expression in both NLC and GLC under TGF-β1 stimulation. Our results demonstrate that miR-29b plays a crucial role in fibrotic remodelling at the LC by antagonising the effects of TGF-β1 on ADAM and ECM gene expression, representing a novel therapeutic target in glaucoma.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

MicroRNA-29b targets ADAM12 and 19 to regulate the extracellular matrix in lamina cribrosa cells

  • 期刊论文

  • 发表日期：

    2025年9月22日

查看全文
  • Aoife Smyth,
  • Breedge Callaghan,
  • Mustapha Irnaten,
  • Darrell Andrews,
  • Colin E. Willoughby,
  • Colm O’Brien

摘要

Glaucoma remains the leading cause of irreversible blindness worldwide, with elevated intraocular pressure (IOP) being the only modifiable risk factor in primary open-angle glaucoma (POAG). Despite adequate IOP control, many patients continue to progress to irreversible optic neuropathy, emphasising the need for alternate treatments. Transforming growth factor-beta (TGF-β) promotes extracellular matrix (ECM) production and fibrosis at the optic nerve head (ONH) in glaucoma. A disintegrin and metalloprotease-12 and metalloprotease-19 (ADAM12 and ADAM19) are implicated in fibrosis. Recent studies have explored miRNA-based manipulation of the TGF-β signalling pathway as a potential therapeutic strategy in fibrosis. This study investigates whether miR-29b modulation affects ADAM12, ADAM19, and ECM gene expression in human lamina cribrosa (LC) cells. Primary human normal lamina cribrosa (NLC) and glaucoma LC (GLC) cells were treated with TGF-β1 and transfected with either a miR-29b mimic or control. Gene expression levels of ADAM12, ADAM19, miR-29b, and several ECM genes were quantified using real-time RT-qPCR, and protein expression levels by Western blotting. ADAM12 and ADAM19 expression was elevated in untreated GLC cells, and treatment with TGF-β1 in both NLC and GLC cells increased ADAM12 and ADAM19 expression. The expression of miR-29b was significantly reduced in both GLC- and TGF-β1-treated NLC and GLC cells. Transfection with miR-29b resulted in a marked reduction in ADAM12 and ADAM19 mRNA expression in TGF-β1-treated NLC and GLC cells. Additionally, miR-29b transfection reduced ECM gene expression in both NLC and GLC under TGF-β1 stimulation. Our results demonstrate that miR-29b plays a crucial role in fibrotic remodelling at the LC by antagonising the effects of TGF-β1 on ADAM and ECM gene expression, representing a novel therapeutic target in glaucoma.