{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:12:30Z","timestamp":1791267150448,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T00:00:00Z","timestamp":1674950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271044"],"award-info":[{"award-number":["82271044"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400396"],"award-info":[{"award-number":["81400396"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["19ZR1408400"],"award-info":[{"award-number":["19ZR1408400"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Shanghai Natural Science Foundation","doi-asserted-by":"publisher","award":["82271044"],"award-info":[{"award-number":["82271044"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Shanghai Natural Science Foundation","doi-asserted-by":"publisher","award":["81400396"],"award-info":[{"award-number":["81400396"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Shanghai Natural Science Foundation","doi-asserted-by":"publisher","award":["19ZR1408400"],"award-info":[{"award-number":["19ZR1408400"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Purpose: To investigate whether asiatic acid (AA) can improve the quantity and function of retinal ganglion cells (RGCs), as well as how AA regulates synaptic pathways in rat models with chronic glaucoma. Methods: In our study, a rat model of chronic glaucoma was prepared via the electrocoagulation of the episcleral veins. The numbers of surviving RGCs were counted via retrograde Fluorogold labeling, and a whole-cell patch clamp was used to clamp RGCs in normal retinal sections and in retinal sections 4 weeks after glaucoma induction. Results: Retrograde-Fluorogold-labeled RGC loss caused by persistent glaucoma was decreased by AA. Additionally, AA reduced the postsynaptic current produced by N-methyl-D-aspartate (NMDA) and diminished miniature glutamatergic excitatory neurotransmission to RGCs. On the other hand, AA increased miniature gamma-aminobutyric acid (GABA)-ergic inhibitory neurotransmission to RGCs and enhanced the GABA-induced postsynaptic current. The excitability of the RGC itself was also decreased by AA. RGCs in glaucomatous slices were less excitable because AA decreased their spontaneous action potential frequency and membrane potential, which led to a hyperpolarized condition. Conclusions: AA directly protected RGCs in a chronic glaucoma rat model by lowering their hyperexcitability. To enhance RGCs\u2019 survival and function in glaucoma, AA may be a viable therapeutic drug.<\/jats:p>","DOI":"10.3390\/jcm12031056","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T01:33:37Z","timestamp":1675042417000},"page":"1056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Differential Modulation of the Excitatory and Inhibitory Synaptic Circuits of Retinal Ganglion Cells via Asiatic Acid in a Chronic Glaucoma Rat Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Yinglei","family":"Zhang","sequence":"first","affiliation":[{"name":"Eye Institute, Eye & ENT Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200032, China"},{"name":"NHC Key Laboratory of Myopia, Eye & ENT Hospital, Fudan University, Shanghai 200032, China"},{"name":"Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Hu","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye & ENT Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200032, China"},{"name":"NHC Key Laboratory of Myopia, Eye & ENT Hospital, Fudan University, Shanghai 200032, China"},{"name":"Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai 200032, China"},{"name":"Department of Pathology, Eye & ENT Hospital, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Huadong Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxu","family":"Hong","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye & ENT Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200032, China"},{"name":"NHC Key Laboratory of Myopia, Eye & ENT Hospital, Fudan University, Shanghai 200032, China"},{"name":"Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xujiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye & ENT Hospital, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200032, China"},{"name":"NHC Key Laboratory of Myopia, Eye & ENT Hospital, Fudan University, Shanghai 200032, China"},{"name":"Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,29]]},"reference":[{"key":"ref_1","first-page":"e11686","article-title":"Epidemiology of glaucoma: The past, present, and predictions for the future","volume":"12","author":"Allison","year":"2020","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.exer.2011.02.017","article-title":"Neuroprotection in glaucoma: Is there a future role of Helicobacter pylori eradication?","volume":"92","author":"Kountouras","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.neuroscience.2009.04.075","article-title":"Combined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucoma","volume":"162","author":"Fu","year":"2009","journal-title":"Neuroscience"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e820","DOI":"10.1038\/cddis.2013.341","article-title":"Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes","volume":"4","author":"Noh","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1097\/IJG.0000000000001906","article-title":"The association between intraocular pressure and visual field worsening in treated glaucoma patients","volume":"30","author":"Yohannan","year":"2021","journal-title":"J. Glaucoma"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/bmc.564","article-title":"Identification of triterpenoid compounds of Centella asiatica by thin-layer chromatography and mass spectrometry","volume":"20","author":"Bonfill","year":"2006","journal-title":"Biomed. Chromatogr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1002\/jnr.22071","article-title":"Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia","volume":"87","author":"Krishnamurthy","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/aps.2012.3","article-title":"Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells","volume":"33","author":"Xu","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1007\/s11064-008-9844-0","article-title":"Protective effects of Asiatic acid on rotenone- or H2O2-induced injury in SH-SY5Y cells","volume":"34","author":"Xiong","year":"2009","journal-title":"Neurochem. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ejphar.2012.01.006","article-title":"Asiatic acid protects primary neurons against C2-ceramide-induced apoptosis","volume":"679","author":"Zhang","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","first-page":"75","article-title":"Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity","volume":"108","author":"Lee","year":"2000","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.jep.2012.07.010","article-title":"Anxiolytic effects of standardized extract of Centella asiatica (ECa 233) after chronic immobilization stress in mice","volume":"143","author":"Wanasuntronwong","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1021\/jm9904349","article-title":"GABA-activated ligand gated ion channels: Medicinal chemistry and molecular biology","volume":"43","author":"Chebib","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0165-0173(97)00061-1","article-title":"Salient features of synaptic organisation in the cerebral cortex","volume":"26","author":"Somogyi","year":"1998","journal-title":"Brain Res. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/cbdd.12766","article-title":"An investigation of the differential effects of ursane triterpenoids from Centella asiatica, and their semisynthetic analogues, on GABAA receptors","volume":"88","author":"Hamid","year":"2016","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1523\/JNEUROSCI.1685-18.2018","article-title":"Activation of 5-HT1A receptors promotes retinal ganglion cell function by inhibiting the cAMP-PKA pathway to modulate presynaptic GABA release in chronic glaucoma","volume":"39","author":"Zhou","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_17","first-page":"3451","article-title":"Retinal damage after 3 to 4 months of elevated intraocular pressure in a rat glaucoma model","volume":"41","author":"Mittag","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1167\/iovs.09-4151","article-title":"Neuroprotective effect of upregulated sonic Hedgehog in retinal ganglion cells following chronic ocular hypertension","volume":"51","author":"Wu","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.nbd.2011.04.019","article-title":"Elevation of p-NR2A(S1232) by Cdk5\/p35 contributes to retinal ganglion cell apoptosis in a rat experimental glaucoma model","volume":"43","author":"Chen","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s004170000241","article-title":"Transforming growth factor-beta 2 levels in aqueous humor of glaucomatous eyes","volume":"239","author":"Inatani","year":"2001","journal-title":"Graefes. Arch. Clin. Exp. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3760\/cma.j.issn.0366-6999.20132398","article-title":"Validation of glaucoma-like features in the rat episcleral vein cauterization model","volume":"127","author":"Bai","year":"2014","journal-title":"Chin. Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s00429-016-1248-3","article-title":"Activation of group I metabotropic glutamate receptors regulates the excitability of rat retinal ganglion cells by suppressing Kir and I h","volume":"222","author":"Li","year":"2016","journal-title":"Brain Struct. Funct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1038\/s41598-017-02092-6","article-title":"Alpha7 nicotinic acetylcholine receptor agonist promotes retinal ganglion cell function via modulating GABAergic presynaptic activity in a chronic glaucomatous model","volume":"7","author":"Zhou","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1038\/cddis.2009.23","article-title":"Structural and functional neuroprotection in glaucoma: Role of galantamine-mediated activation of muscarinic acetylcholine receptors","volume":"1","author":"Almasieh","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3389\/fnins.2018.00489","article-title":"Asiatic acid prevents retinal ganglion cell apoptosis in a rat model of glaucoma","volume":"12","author":"Huang","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.exer.2016.08.006","article-title":"Evaluating retinal ganglion cell loss and dysfunction","volume":"151","author":"Mead","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1364\/BOE.4.000364","article-title":"Imaging axonal transport in the rat visual pathway","volume":"4","author":"Abbott","year":"2013","journal-title":"Biomed. Opt. Express"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pbr.2015.04.008","article-title":"Retinal neurodegeneration in experimental glaucoma","volume":"220","year":"2015","journal-title":"Prog. Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/OPX.0b013e31817841cb","article-title":"Mechanical environment of the optic nerve head in glaucoma","volume":"85","author":"Downs","year":"2008","journal-title":"Optom. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2015.03.002","article-title":"Autophagy in axonal degeneration in glaucomatous optic neuropathy","volume":"47","author":"Munemasa","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.phymed.2011.10.004","article-title":"Inhibitory effect of Asiatic acid on acetylcholinesterase, excitatory post synaptic potential and locomotor activity","volume":"19","author":"Nasir","year":"2012","journal-title":"Phytomedicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0304-3940(90)90236-3","article-title":"GABAB agonists modulate a transient potassium current in cultured mammalian hippocampal neurons","volume":"118","author":"Saint","year":"1990","journal-title":"Neurosci. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e01093","DOI":"10.1002\/brb3.1093","article-title":"Hippocampal amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid GluA1 (AMPA GluA1) receptor subunit involves in learning and memory improvement following treatment with Centella asiatica extract in adolescent rats","volume":"8","author":"Muthuraju","year":"2018","journal-title":"Brain Behav."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/3\/1056\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:19:25Z","timestamp":1760120365000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/3\/1056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,29]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jcm12031056"],"URL":"https:\/\/doi.org\/10.3390\/jcm12031056","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,29]]}}}