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Abstract #100308 Published in IGR 23-1
Atorvastatin reduces IOP in ocular hypertension and suppresses ECM in trabecular meshwork perhaps via FGD4
Song XY; Chen YY; Liu WT; Cong L; Zhang JL; Zhang Y; Zhang YYInternational Journal of Molecular Medicine 2022; 49:
To explore the role of atorvastatin in regulating intraocular pressure (IOP) in glaucoma , and to investigate its related molecular pathway , an ocular hypertension model was generated by intravitreal injection of an adenoviral vector encoding transforming growth factor (TGF)‑β2 in the right eye of BALB/cJ mice, while the left was treated with an empty control adenovirus. To determine its anti‑intraocular hypertension role, these induced hyper‑IOP mice were gavaged with atorvastatin (20 mg/kg/day). Furthermore, extracellular matrix (ECM) factors were examined in the primary human trabecular meshwork (HTM) cells followed atorvastatin (0~200 µM) treatment . Whole genome microarray was employed to identify potential therapeutic target molecules associated with ECM regulation. Unilateral murine ocular hypertension was induced, via intravitreal injection of the adenoviral vector carrying the human TGF‑β2 gene (Ad.hTGF‑β2), raising IOP from 12±1.6 to 32.3±0.7 mmHg (n=6, P<0.05) at day 15, which plateaued from day 15 to 30. Atorvastatin administration from day 15 to 30 decreased IOP from 32.3±0.7 to 15.4±1.1 mmHg (n=6, P<0.05) at day 30. Additionally, atorvastatin administration changed the morphology of cultured HTM cells from an elongated and adherent morphology into rounded, less elongated and less adherent cells, accompanied with suppressed expression of ECM. Gene Ontology and Genome analysis revealed that FGD4 (FYVE, RhoGEF and PH domain containing 4) might be a key factor contributing to these changes. Our data demonstrated that atorvastatin reduced TGF‑β2‑induced ocular hypertension , perhaps via modifying cellular structure and decreasing ECM, using the FGD4 signaling pathway, as demonstrated in HTM cells. Our findings provide some useful information for the management of glaucoma, with statin therapy revealing a potential novel therapeutic pathway for glaucoma treatment.
Department of Ophthalmology, Huadong Hospital, Fudan University, Shanghai 200040, P.R. China.
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