Astragaloside IV Attenuates Ocular Hypertension in a Mouse Model of TGFβ2 Induced Primary Open Angle Glaucoma
Abstract
:1. Introduction
2. Results
2.1. Astragaloside IV Treatment Attenuates the TGFβ2 Induced Fibrotic Changes and ER Stress in TM Cells
2.2. Astragaloside IV Treatment Inhibits TGFβ2 Induced NF-κB Activation and αSMA Expression in TM Cells
2.3. Antifibrotic Effects of AS.IV Are Mediated via Increased Metalloproteases Activity in TM Cells
2.4. Astragaloside IV Treatment Effectively Decreases Mutant Myocilin Associated ER Stress in the TM Cells
2.5. Astragaloside IV Treatment Reversed the TGFβ2 Induced Ocular Hypertension in the Mice
3. Discussion
4. Materials and Methods
4.1. Antibodies and Reagents
4.2. TM Cell Culture and Treatments
4.3. Gelatin Zymography
4.4. Experimental Animals
4.6. IOP Measurements
4.7. Western Blot Analysis
4.8. Immunostaining
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Tham, Y.C.; Li, X.; Wong, T.Y.; Quigley, H.A.; Aung, T.; Cheng, C.Y. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology 2014, 121, 2081–2090. [Google Scholar] [CrossRef] [PubMed]
- Quigley, H.A.; Broman, A.T. The number of people with glaucoma worldwide in 2010 and 2020. Br. J. Ophthalmol. 2006, 90, 262–267. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rosenthal, J.; Leske, M.C. Open-angle glaucoma risk factors applied to clinical area. J. Am. Optom. Assoc. 1980, 51, 1017–1024. [Google Scholar]
- Kwon, Y.H.; Fingert, J.H.; Kuehn, M.H.; Alward, W.L. Primary open-angle glaucoma. N. Engl. J. Med. 2009, 360, 1113–1124. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rohen, J.W. Why is intraocular pressure elevated in chronic simple glaucoma? Anatomical considerations. Ophthalmology 1983, 90, 758–765. [Google Scholar] [CrossRef]
- Acott, T.S.; Kelley, M.J. Extracellular matrix in the trabecular meshwork. Exp. Eye Res. 2008, 86, 543–561. [Google Scholar] [CrossRef] [Green Version]
- Keller, K.E.; Aga, M.; Bradley, J.M.; Kelley, M.J.; Acott, T.S. Extracellular matrix turnover and outflow resistance. Exp. Eye Res. 2009, 88, 676–682. [Google Scholar] [CrossRef] [Green Version]
- Tamm, E.R. The trabecular meshwork outflow pathways: Structural and functional aspects. Exp. Eye Res. 2009, 88, 648–655. [Google Scholar] [CrossRef] [PubMed]
- Kasetti, R.B.; Phan, T.N.; Millar, J.C.; Zode, G.S. Expression of Mutant Myocilin Induces Abnormal Intracellular Accumulation of Selected Extracellular Matrix Proteins in the Trabecular Meshwork. Investig. Ophthalmol. Vis. Sci. 2016, 57, 6058–6069. [Google Scholar] [CrossRef] [Green Version]
- Kasetti, R.B.; Patel, P.D.; Maddineni, P.; Patil, S.; Kiehlbauch, C.; Millar, J.C.; Searby, C.C.; Raghunathan, V.; Sheffield, V.C.; Zode, G.S. ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load. Nat. Commun. 2020, 11, 5594. [Google Scholar] [CrossRef]
- Kasetti, R.B.; Patel, P.D.; Maddineni, P.; Zode, G.S. Ex-vivo cultured human corneoscleral segment model to study the effects of glaucoma factors on trabecular meshwork. PLoS ONE 2020, 15, e0232111. [Google Scholar] [CrossRef]
- Patel, G.C.; Phan, T.N.; Maddineni, P.; Kasetti, R.B.; Millar, J.C.; Clark, A.F.; Zode, G.S. Dexamethasone-Induced Ocular Hypertension in Mice: Effects of Myocilin and Route of Administration. Am. J. Pathol. 2017, 187, 713–723. [Google Scholar] [CrossRef] [Green Version]
- Jain, A.; Zode, G.; Kasetti, R.B.; Ran, F.A.; Yan, W.; Sharma, T.P.; Bugge, K.; Searby, C.C.; Fingert, J.H.; Zhang, F.; et al. CRISPR-Cas9-based treatment of myocilin-associated glaucoma. Proc. Natl. Acad. Sci. USA 2017, 114, 11199–11204. [Google Scholar] [CrossRef] [Green Version]
- Kasetti, R.B.; Maddineni, P.; Patel, P.D.; Searby, C.; Sheffield, V.C.; Zode, G.S. Transforming growth factor beta2 (TGFbeta2) signaling plays a key role in glucocorticoid-induced ocular hypertension. J. Biol. Chem. 2018, 293, 9854–9868. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kasetti, R.B.; Maddineni, P.; Millar, J.C.; Clark, A.F.; Zode, G.S. Increased synthesis and deposition of extracellular matrix proteins leads to endoplasmic reticulum stress in the trabecular meshwork. Sci. Rep. 2017, 7, 14951. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Inatani, M.; Tanihara, H.; Katsuta, H.; Honjo, M.; Kido, N.; Honda, Y. Transforming growth factor-beta 2 levels in aqueous humor of glaucomatous eyes. Graefes. Arch. Clin. Exp. Ophthalmol. 2001, 239, 109–113. [Google Scholar] [CrossRef] [PubMed]
- Ozcan, A.A.; Ozdemir, N.; Canataroglu, A. The aqueous levels of TGF-beta2 in patients with glaucoma. Int. Ophthalmol. 2004, 25, 19–22. [Google Scholar] [CrossRef]
- Ochiai, Y.; Ochiai, H. Higher concentration of transforming growth factor-beta in aqueous humor of glaucomatous eyes and diabetic eyes. Jpn. J. Ophthalmol. 2002, 46, 249–253. [Google Scholar] [CrossRef]
- Tripathi, R.C.; Li, J.; Chan, W.F.; Tripathi, B.J. Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2. Exp. Eye Res. 1994, 59, 723–727. [Google Scholar] [CrossRef]
- Fleenor, D.L.; Shepard, A.R.; Hellberg, P.E.; Jacobson, N.; Pang, I.H.; Clark, A.F. TGFbeta2-induced changes in human trabecular meshwork: Implications for intraocular pressure. Invest. Ophthalmol. Vis. Sci. 2006, 47, 226–234. [Google Scholar] [CrossRef] [Green Version]
- Takahashi, E.; Inoue, T.; Fujimoto, T.; Kojima, S.; Tanihara, H. Epithelial mesenchymal transition-like phenomenon in trabecular meshwork cells. Exp. Eye Res. 2014, 118, 72–79. [Google Scholar] [CrossRef]
- Pattabiraman, P.P.; Rao, P.V. Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells. Am. J. Physiol. Cell Physiol. 2010, 298, C749–C763. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wordinger, R.J.; Fleenor, D.L.; Hellberg, P.E.; Pang, I.H.; Tovar, T.O.; Zode, G.S.; Fuller, J.A.; Clark, A.F. Effects of TGF-beta2, BMP-4, and gremlin in the trabecular meshwork: Implications for glaucoma. Investig. Ophthalmol. Vis. Sci. 2007, 48, 1191–1200. [Google Scholar] [CrossRef]
- Shepard, A.R.; Millar, J.C.; Pang, I.H.; Jacobson, N.; Wang, W.H.; Clark, A.F. Adenoviral gene transfer of active human transforming growth factor-{beta}2 elevates intraocular pressure and reduces outflow facility in rodent eyes. Investig. Ophthalmol. Vis. Sci. 2010, 51, 2067–2076. [Google Scholar] [CrossRef] [Green Version]
- McDowell, C.M.; Tebow, H.E.; Wordinger, R.J.; Clark, A.F. Smad3 is necessary for transforming growth factor-beta2 induced ocular hypertension in mice. Exp. Eye Res. 2013, 116, 419–423. [Google Scholar] [CrossRef] [Green Version]
- Gottanka, J.; Chan, D.; Eichhorn, M.; Lutjen-Drecoll, E.; Ethier, C.R. Effects of TGF-beta2 in perfused human eyes. Investig. Ophthalmol. Vis. Sci. 2004, 45, 153–158. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, G.; Lee, C.; Read, A.T.; Wang, K.; Ha, J.; Kuhn, M.; Navarro, I.; Cui, J.; Young, K.; Gorijavolu, R.; et al. Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis. Elife 2021, 10, e60831. [Google Scholar] [CrossRef]
- Winkler, N.S.; Fautsch, M.P. Effects of prostaglandin analogues on aqueous humor outflow pathways. J. Ocul. Pharmacol. Ther. 2014, 30, 102–109. [Google Scholar] [CrossRef] [Green Version]
- Linden, C.; Alm, A. Prostaglandin analogues in the treatment of glaucoma. Drugs Aging 1999, 14, 387–398. [Google Scholar] [CrossRef] [PubMed]
- Tejwani, S.; Machiraju, P.; Nair, A.P.; Ghosh, A.; Das, R.K.; Ghosh, A.; Sethu, S. Treatment of glaucoma by prostaglandin agonists and beta-blockers in combination directly reduces pro-fibrotic gene expression in trabecular meshwork. J. Cell Mol. Med. 2020, 24, 5195–5204. [Google Scholar] [CrossRef] [Green Version]
- Igarashi, N.; Honjo, M.; Aihara, M. mTOR inhibitors potentially reduce TGF-beta2-induced fibrogenic changes in trabecular meshwork cells. Sci. Rep. 2021, 11, 14111. [Google Scholar] [CrossRef]
- Kasetti, R.B.; Maddineni, P.; Kiehlbauch, C.C.; Patil, S.; Searby, C.C.; Levine, B.; Sheffield, V.C.; Zode, G.S. Autophagy stimulation reduces ocular hypertension in murine glaucoma model via autophagic degradation of mutant myocilin. JCI Insight. 2021, 6, e143359. [Google Scholar] [CrossRef] [PubMed]
- Zode, G.S.; Kuehn, M.H.; Nishimura, D.Y.; Searby, C.C.; Mohan, K.; Grozdanic, S.D.; Bugge, K.; Anderson, M.G.; Clark, A.F.; Stone, E.M.; et al. Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma. J. Clin. Investig. 2011, 121, 3542–3553. [Google Scholar] [CrossRef] [Green Version]
- Zode, G.S.; Sharma, A.B.; Lin, X.; Searby, C.C.; Bugge, K.; Kim, G.H.; Clark, A.F.; Sheffield, V.C. Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma. J. Clin. Investig. 2014, 124, 1956–1965. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maddineni, P.; Kasetti, R.B.; Kodati, B.; Yacoub, S.; Zode, G.S. Sodium 4-Phenylbutyrate Reduces Ocular Hypertension by Degrading Extracellular Matrix Deposition via Activation of MMP9. Int. J. Mol. Sci. 2021, 22, 10095. [Google Scholar] [CrossRef]
- Newman, D.J.; Cragg, G.M. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J. Nat. Prod. 2020, 83, 770–803. [Google Scholar] [CrossRef] [PubMed]
- Chen, P.; Xie, Y.; Shen, E.; Li, G.G.; Yu, Y.; Zhang, C.B.; Yang, Y.; Zou, Y.; Ge, J.; Chen, R.; et al. Astragaloside IV attenuates myocardial fibrosis by inhibiting TGF-beta1 signaling in coxsackievirus B3-induced cardiomyopathy. Eur. J. Pharmacol. 2011, 658, 168–174. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.; Wei, W.; Sun, W.Y.; Li, X. Protective effects of astragaloside IV on porcine-serum-induced hepatic fibrosis in rats and in vitro effects on hepatic stellate cells. J. Ethnopharmacol. 2009, 122, 502–508. [Google Scholar] [CrossRef]
- Wang, L.; Chi, Y.F.; Yuan, Z.T.; Zhou, W.C.; Yin, P.H.; Zhang, X.M.; Peng, W.; Cai, H. Astragaloside IV inhibits renal tubulointerstitial fibrosis by blocking TGF-beta/Smad signaling pathway in vivo and in vitro. Exp. Biol. Med. 2014, 239, 1310–1324. [Google Scholar] [CrossRef]
- Dong, Z.; Zhou, J.; Zhang, Y.; Chen, Y.; Yang, Z.; Huang, G.; Chen, Y.; Yuan, Z.; Peng, Y.; Cao, T. Astragaloside-IV Alleviates Heat-Induced Inflammation by Inhibiting Endoplasmic Reticulum Stress and Autophagy. Cell Physiol. Biochem. 2017, 42, 824–837. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guo, H.; Wang, Y.; Zhang, X.; Zang, Y.; Zhang, Y.; Wang, L.; Wang, H.; Wang, Y.; Cao, A.; Peng, W. Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKalpha-regulated autophagy induction in streptozotocin-induced diabetic nephropathy. Sci. Rep. 2017, 7, 6852. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, Y.; Li, Q.; Zhao, W.; Li, J.; Sun, Y.; Liu, K.; Liu, B.; Zhang, N. Astragaloside IV and cycloastragenol are equally effective in inhibition of endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation in the endothelium. J. Ethnopharmacol. 2015, 169, 210–218. [Google Scholar] [CrossRef] [PubMed]
- Zhou, B.; Zhou, D.L.; Wei, X.H.; Zhong, R.Y.; Xu, J.; Sun, L. Astragaloside IV attenuates free fatty acid-induced ER stress and lipid accumulation in hepatocytes via AMPK activation. Acta Pharmacol. Sin. 2017, 38, 998–1008. [Google Scholar] [CrossRef] [Green Version]
- Chen, Y.; Gui, D.; Chen, J.; He, D.; Luo, Y.; Wang, N. Down-regulation of PERK-ATF4-CHOP pathway by Astragaloside IV is associated with the inhibition of endoplasmic reticulum stress-induced podocyte apoptosis in diabetic rats. Cell Physiol. Biochem. 2014, 33, 1975–1987. [Google Scholar] [CrossRef] [PubMed]
- Li, L.; Hou, X.; Xu, R.; Liu, C.; Tu, M. Research review on the pharmacological effects of astragaloside IV. Fundam. Clin. Pharmacol. 2017, 31, 17–36. [Google Scholar] [CrossRef]
- Xu, M.; Yin, J.; Xie, L.; Zhang, J.; Zou, C.; Zou, J.; Liu, F.; Ju, W.; Li, P. Pharmacokinetics and tolerance of toal astragalosides after intravenous infusion of astragalosides injection in healthy Chinese volunteers. Phytomedicine 2013, 20, 1105–1111. [Google Scholar] [CrossRef] [PubMed]
- Hernandez, H.; Roberts, A.L.; McDowell, C.M. Nuclear factor-kappa beta signaling is required for transforming growth factor Beta-2 induced ocular hypertension. Exp. Eye Res. 2020, 191, 107920. [Google Scholar] [CrossRef] [PubMed]
- Hsieh, H.L.; Liu, S.H.; Chen, Y.L.; Huang, C.Y.; Wu, S.J. Astragaloside IV suppresses inflammatory response via suppression of NF-kappaB, and MAPK signalling in human bronchial epithelial cells. Arch. Physiol. Biochem. 2020, 1–10. [Google Scholar] [CrossRef]
- Zhang, W.J.; Frei, B. Astragaloside IV inhibits NF- kappa B activation and inflammatory gene expression in LPS-treated mice. Mediators Inflamm. 2015, 2015, 274314. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, W.J.; Hufnagl, P.; Binder, B.R.; Wojta, J. Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-kappaB activation and adhesion molecule expression. Thromb. Haemost. 2003, 90, 904–914. [Google Scholar] [CrossRef] [PubMed]
- Torrejon, K.Y.; Papke, E.L.; Halman, J.R.; Bergkvist, M.; Danias, J.; Sharfstein, S.T.; Xie, Y. TGFbeta2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor. Sci. Rep. 2016, 6, 38319. [Google Scholar] [CrossRef] [Green Version]
- De Groef, L.; Van Hove, I.; Dekeyster, E.; Stalmans, I.; Moons, L. MMPs in the trabecular meshwork: Promising targets for future glaucoma therapies? Investig. Ophthalmol. Vis. Sci. 2013, 54, 7756–7763. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stone, E.M.; Fingert, J.H.; Alward, W.L.; Nguyen, T.D.; Polansky, J.R.; Sunden, S.L.; Nishimura, D.; Clark, A.F.; Nystuen, A.; Nichols, B.E.; et al. Identification of a gene that causes primary open angle glaucoma. Science 1997, 275, 668–670. [Google Scholar] [CrossRef] [PubMed]
- Rocha-Sousa, A.; Rodrigues-Araujo, J.; Gouveia, P.; Barbosa-Breda, J.; Azevedo-Pinto, S.; Pereira-Silva, P.; Leite-Moreira, A. New therapeutic targets for intraocular pressure lowering. ISRN Ophthalmol. 2013, 2013, 261386. [Google Scholar] [CrossRef] [Green Version]
- Yang, Y.; Abdulatef, A.; Zhang, L.; Jiang, H.; Zeng, Z.; Li, H.; Xia, X. Cross-talk between MYOC p. Y437H mutation and TGF-beta2 in the pathology of glaucoma. Int. J. Med. Sci. 2020, 17, 1062–1070. [Google Scholar] [CrossRef] [PubMed]
- Che, X.; Wang, Q.; Xie, Y.; Xu, W.; Shao, X.; Mou, S.; Ni, Z. Astragaloside IV suppresses transforming growth factor-beta1 induced fibrosis of cultured mouse renal fibroblasts via inhibition of the MAPK and NF-kappaB signaling pathways. Biochem. Biophys. Res. Commun. 2015, 464, 1260–1266. [Google Scholar] [CrossRef] [PubMed]
- Zhou, X.; Sun, X.; Gong, X.; Yang, Y.; Chen, C.; Shan, G.; Yao, Q. Astragaloside IV from Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting inflammation via TLR4/NF-small ka, CyrillicB in vivo and in vitro. Int. Immunopharmacol. 2017, 42, 18–24. [Google Scholar] [CrossRef]
- Seki, E.; De Minicis, S.; Osterreicher, C.H.; Kluwe, J.; Osawa, Y.; Brenner, D.A.; Schwabe, R.F. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat. Med. 2007, 13, 1324–1332. [Google Scholar] [CrossRef] [PubMed]
- Bhattacharyya, S.; Kelley, K.; Melichian, D.S.; Tamaki, Z.; Fang, F.; Su, Y.; Feng, G.; Pope, R.M.; Budinger, G.R.; Mutlu, G.M.; et al. Toll-like receptor 4 signaling augments transforming growth factor-beta responses: A novel mechanism for maintaining and amplifying fibrosis in scleroderma. Am. J. Pathol. 2013, 182, 192–205. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hernandez, H.; Medina-Ortiz, W.E.; Luan, T.; Clark, A.F.; McDowell, C.M. Crosstalk Between Transforming Growth Factor Beta-2 and Toll-Like Receptor 4 in the Trabecular Meshwork. Investig. Ophthalmol. Vis. Sci. 2017, 58, 1811–1823. [Google Scholar] [CrossRef] [Green Version]
- Yan, X.; Lin, Z.; Chen, F.; Zhao, X.; Chen, H.; Ning, Y.; Chen, Y.G. Human BAMBI cooperates with Smad7 to inhibit transforming growth factor-beta signaling. J. Biol. Chem. 2009, 284, 30097–30104. [Google Scholar] [CrossRef] [Green Version]
- Samples, J.R.; Alexander, J.P.; Acott, T.S. Regulation of the levels of human trabecular matrix metalloproteinases and inhibitor by interleukin-1 and dexamethasone. Investig. Ophthalmol. Vis. Sci. 1993, 34, 3386–3395. [Google Scholar] [PubMed]
- Alexander, J.P.; Samples, J.R.; Van Buskirk, E.M.; Acott, T.S. Expression of matrix metalloproteinases and inhibitor by human trabecular meshwork. Investig. Ophthalmol. Vis. Sci. 1991, 32, 172–180. [Google Scholar] [PubMed]
- Bradley, J.M.; Vranka, J.; Colvis, C.M.; Conger, D.M.; Alexander, J.P.; Fisk, A.S.; Samples, J.R.; Acott, T.S. Effect of matrix metalloproteinases activity on outflow in perfused human organ culture. Investig. Ophthalmol. Vis. Sci. 1998, 39, 2649–2658. [Google Scholar] [PubMed]
- Fuchshofer, R.; Welge-Lussen, U.; Lutjen-Drecoll, E. The effect of TGF-beta2 on human trabecular meshwork extracellular proteolytic system. Exp. Eye Res. 2003, 77, 757–765. [Google Scholar] [CrossRef]
- Bradley, J.M.; Kelley, M.J.; Zhu, X.; Anderssohn, A.M.; Alexander, J.P.; Acott, T.S. Effects of mechanical stretching on trabecular matrix metalloproteinases. Investig. Ophthalmol. Vis. Sci. 2001, 42, 1505–1513. [Google Scholar]
- De Groef, L.; Andries, L.; Siwakoti, A.; Geeraerts, E.; Bollaerts, I.; Noterdaeme, L.; Etienne, I.; Papageorgiou, A.P.; Stalmans, I.; Billen, J.; et al. Aberrant Collagen Composition of the Trabecular Meshwork Results in Reduced Aqueous Humor Drainage and Elevated IOP in MMP-9 Null Mice. Investig. Ophthalmol. Vis. Sci. 2016, 57, 5984–5995. [Google Scholar] [CrossRef]
- Tian, B.; Geiger, B.; Epstein, D.L.; Kaufman, P.L. Cytoskeletal involvement in the regulation of aqueous humor outflow. Investig. Ophthalmol. Vis. Sci. 2000, 41, 619–623. [Google Scholar]
- Bermudez, J.Y.; Montecchi-Palmer, M.; Mao, W.; Clark, A.F. Cross-linked actin networks (CLANs) in glaucoma. Exp. Eye Res. 2017, 159, 16–22. [Google Scholar] [CrossRef] [PubMed]
- Yuan, X.; Gong, Z.; Wang, B.; Guo, X.; Yang, L.; Li, D.; Zhang, Y. Astragaloside Inhibits Hepatic Fibrosis by Modulation of TGF-beta1/Smad Signaling Pathway. Evid.-Based Complement. Alternat. Med. 2018, 2018, 3231647. [Google Scholar] [CrossRef] [Green Version]
- Peters, J.C.; Bhattacharya, S.; Clark, A.F.; Zode, G.S. Increased Endoplasmic Reticulum Stress in Human Glaucomatous Trabecular Meshwork Cells and Tissues. Investig. Ophthalmol. Vis. Sci. 2015, 56, 3860–3868. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hou, B.; Liu, R.; Wu, Y.; Huang, S. Astragaloside IV Reduces Cerebral Ischemia/Reperfusion-Induced Blood-Brain Barrier Permeability in Rats by Inhibiting ER Stress-Mediated Apoptosis. Evid.-Based. Complement. Alternat. Med. 2020, 2020, 9087873. [Google Scholar] [CrossRef] [PubMed]
- Ju, Y.; Su, Y.; Chen, Q.; Ma, K.; Ji, T.; Wang, Z.; Li, W.; Li, W. Protective effects of Astragaloside IV on endoplasmic reticulum stress-induced renal tubular epithelial cells apoptosis in type 2 diabetic nephropathy rats. Biomed. Pharmacother. 2019, 109, 84–92. [Google Scholar] [CrossRef] [PubMed]
- Keller, K.E.; Bhattacharya, S.K.; Borras, T.; Brunner, T.M.; Chansangpetch, S.; Clark, A.F.; Dismuke, W.M.; Du, Y.; Elliott, M.H.; Ethier, C.R.; et al. Consensus recommendations for trabecular meshwork cell isolation, characterization and culture. Exp. Eye Res. 2018, 171, 164–173. [Google Scholar] [CrossRef] [PubMed]
- Wang, W.H.; Millar, J.C.; Pang, I.H.; Wax, M.B.; Clark, A.F. Noninvasive measurement of rodent intraocular pressure with a rebound tonometer. Investig. Ophthalmol. Vis. Sci. 2005, 46, 4617–4621. [Google Scholar] [CrossRef] [PubMed] [Green Version]
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Kasetti, R.B.; Maddineni, P.; Kodati, B.; Nagarajan, B.; Yacoub, S. Astragaloside IV Attenuates Ocular Hypertension in a Mouse Model of TGFβ2 Induced Primary Open Angle Glaucoma. Int. J. Mol. Sci. 2021, 22, 12508. https://doi.org/10.3390/ijms222212508
Kasetti RB, Maddineni P, Kodati B, Nagarajan B, Yacoub S. Astragaloside IV Attenuates Ocular Hypertension in a Mouse Model of TGFβ2 Induced Primary Open Angle Glaucoma. International Journal of Molecular Sciences. 2021; 22(22):12508. https://doi.org/10.3390/ijms222212508
Chicago/Turabian StyleKasetti, Ramesh B., Prabhavathi Maddineni, Bindu Kodati, Bhavani Nagarajan, and Sam Yacoub. 2021. "Astragaloside IV Attenuates Ocular Hypertension in a Mouse Model of TGFβ2 Induced Primary Open Angle Glaucoma" International Journal of Molecular Sciences 22, no. 22: 12508. https://doi.org/10.3390/ijms222212508