2. Academic Validation
  3. Eye Drops of Metformin Prevents Fibrosis After Glaucoma Filtration Surgery in Rats via Activating AMPK/Nrf2 Signaling Pathway

Eye Drops of Metformin Prevents Fibrosis After Glaucoma Filtration Surgery in Rats via Activating AMPK/Nrf2 Signaling Pathway

  • Front Pharmacol. 2020 Jul 31;11:1038. doi: 10.3389/fphar.2020.01038.
Xueru Li 1,  Yu Leng 1,  Qingzhi Jiang 2,  Ziwen Wang 3,  Peng Luo 3,  Chi Zhang 3,  Long Chen 3,  Yawei Wang 3,  Huilan Wang 2,  Xiaofeng Yue 4,  Chongxing Shen 4,  Yuanlinhan Zhou 5,  Chunmeng Shi 3,  Lin Xie 1
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China.
  • 2 Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
  • 3 Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China.
  • 4 Department of Urology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China.
  • 5 Chongqing Industry Polytechnic College, Chongqing, China.
PMID: 32903813 DOI: 10.3389/fphar.2020.01038
Abstract

Metformin has effective therapeutic effects in anti-tumor and anti-fibrotic diseases. However, how the antifibrotic effect of metformin in the eye and how it is transferred are still unclear. Here, the eye drop of metformin treatment was studied in Sprague-Dawley (SD) rats of glaucoma filtrating surgery (GFS). Rats were administered randomly bilateral drops: control group (without surgery), GFS group, metformin group or mitomycin C (MMC) group (Sponge application intraoperatively, 0.02%). Bleb features and intraocular pressure (IOP) were assessed for postoperative week 4. Metformin effectively inhibited fibrosis and improved the surgical outcomes of GFS. In vitro, we found that the degree of oxidative stress and fibrosis in metformin pretreated-Human Conjunctival Fibroblasts (HConFs) were reduced; the pro-fibrotic response of HConFs were decreased by inducing macrophagic polarity changes. Besides, the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2)/AMP-activated protein kinase (AMPK) and the competition of organic cation transporters (OCTs) effectively reduced the anti-fibrotic capability of metformin. Together, this experiment indicates that metformin enters into HConFs cell with OCTs, which can protect against filtrating blebs scar formation in SD rats of GFS via activating AMPK/Nrf2 axis and the downregulation of profibrogenic and inflammatory biomarkers.

Keywords

AMPK/Nrf2; fibrosis; glaucoma filtration surgery (GFS); macrophages; metformin; organic cation transporters (OCTs); oxidative stress.

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