{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:14:21Z","timestamp":1781100861823,"version":"3.54.1"},"reference-count":80,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,15]],"date-time":"2021-08-15T00:00:00Z","timestamp":1628985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Background: Glaucoma is currently the leading cause of irreversible blindness; it is a neuropathy characterized by structural alterations of the optic nerve, leading to visual impairments. The aim of this work is to develop a new oral formulation able to counteract the early changes connected to glaucomatous degeneration. The composition is based on gastrodin and vitamin D3 combined with vitamin C, blackcurrant, and lycopene. Methods: Cells and tissues of the retina were used to study biological mechanisms involved in glaucoma, to slow down the progression of the disease. Experiments mimicking the conditions of glaucoma were carried out to examine the etiology of retinal degeneration. Results: Our results show a significant ability to restore glaucoma-induced damage, by counteracting ROS production and promoting cell survival by inhibiting apoptosis. These effects were confirmed by the intracellular mechanism that was activated following administration of the compound, either before or after the glaucoma induction. In particular, the main results were obtained as a preventive action of glaucoma, showing a beneficial action on all selected markers, both on cells and on eyecup preparations. It is therefore possible to hypothesize both the preventive and therapeutic use of this formulation, in the presence of risk factors, and due to its ability to inhibit the apoptotic cycle and to stimulate cell survival mechanisms, respectively. Conclusion: This formulation has exhibited an active role in the prevention or restoration of glaucoma damage for the first time.<\/jats:p>","DOI":"10.3390\/foods10081885","type":"journal-article","created":{"date-parts":[[2021,8,15]],"date-time":"2021-08-15T21:43:55Z","timestamp":1629063835000},"page":"1885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of a New Combination of Natural Extracts on Glaucoma-Related Retinal Degeneration"],"prefix":"10.3390","volume":"10","author":[{"given":"Claudio","family":"Molinari","sequence":"first","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ruga","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahitab","family":"Farghali","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Galla","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Fernandez-Godino","sequence":"additional","affiliation":[{"name":"Ocular Genomics Institute-Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nausicaa","family":"Clemente","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute, Interdisciplinary Research Center of Autoimmune Diseases-IRCAD, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5751-270X","authenticated-orcid":false,"given":"Francesca","family":"Uberti","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,15]]},"reference":[{"key":"ref_1","unstructured":"Silvio, P. (2012). Global Data on Visual Impairments 2010, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s11892-016-0815-6","article-title":"Presence and Risk Factors for Glaucoma in Patients with Diabetes","volume":"16","author":"Song","year":"2016","journal-title":"Curr. Diabetes Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.2147\/DDDT.S80594","article-title":"Neuroprotective therapies for glaucoma","volume":"9","author":"Song","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.2174\/1570159X15666171109124520","article-title":"Rational Basis for Nutraceuticals in the Treatment of Glaucoma","volume":"16","author":"Morrone","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_5","first-page":"35","article-title":"Glaucoma: Epidemiologia molecolare, patogenesi, prevenzione","volume":"97","author":"Izzotti","year":"2006","journal-title":"Recenti Progressi Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sacc\u00e0, S.C., Corazza, P., Gandolfi, S., Ferrari, D., Sukkar, S., Iorio, E.L., and Traverso, C.E. (2019). Substances of Interest That Support Glaucoma Therapy. Nutrients, 11.","DOI":"10.3390\/nu11020239"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e04408","DOI":"10.1016\/j.heliyon.2020.e04408","article-title":"The potential health benefits of dietary natural plant products in age related eye diseases","volume":"10","author":"Ikonne","year":"2020","journal-title":"Heliyon"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1167\/iovs.03-0948","article-title":"Glutamate-induced glutamine synthetase expression in retinal Muller cells after short-term ocular hypertension in the rat","volume":"45","author":"Shen","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1136\/bjo.2003.028357","article-title":"Nitric oxide proxies and ocular perfusion pressure in primary open angle glaucoma","volume":"88","author":"Galassi","year":"2004","journal-title":"Br. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1016\/S0039-6257(99)00050-8","article-title":"Vascular aspects in the pathophysiology of glaucomatous optic neuropathy","volume":"43","author":"Chung","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13167-015-0043-1","article-title":"Retinal venous pressure: The role of endothelin","volume":"6","author":"Flammer","year":"2015","journal-title":"EPMA J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.mrrev.2005.11.001","article-title":"The role of oxidative stress in glaucoma","volume":"612","author":"Izzotti","year":"2006","journal-title":"Mutat. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ejphar.2016.03.064","article-title":"Retinal ganglion cell death in glaucoma: Exploring the role of neuroinflammation","volume":"787","author":"Russo","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s40478-018-0618-x","article-title":"EphrinB\/EphB forward signaling in M\u00fcller cells causes apoptosis of retinal ganglion cells by increasing tumor necrosis factor alpha production in rat experimental glaucomatous model","volume":"24","author":"Liu","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2147\/OPTH.S192010","article-title":"Effect of systemic antihypertensives on change in intraocular pressure after initiating topical prostaglandins for primary open-angle glaucoma","volume":"23","author":"Siddiqui","year":"2019","journal-title":"Clin. Ophthalmol."},{"key":"ref_16","first-page":"115","article-title":"Implications for postoperative visual loss: Steep Trendelenburg position and effects on intraocular pressure","volume":"79","author":"Molloy","year":"2011","journal-title":"Am. Assoc. Nurse Anesth. J."},{"key":"ref_17","unstructured":"European Glaucoma Society (2003). Terminology and Guidelines for Glaucoma, Dogma SRL."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"959","DOI":"10.2174\/1570159X15666170724104305","article-title":"Neuroprotection by (endo) Cannabinoids in Glaucoma and Retinal Neurodegenerative Diseases","volume":"16","author":"Rapino","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.cell.2020.03.037","article-title":"Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema","volume":"181","author":"Kitchen","year":"2020","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"183573","DOI":"10.1016\/j.bbamem.2021.183573","article-title":"The effects of trifluoperazine on brain edema, aquaporin-4 expression and metabolic markers during the acute phase of stroke using photothrombotic mouse model","volume":"1863","author":"Sylvain","year":"2021","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1146\/annurev.neuro.23.1.579","article-title":"The relationship between neuronal survival and regeneration","volume":"23","author":"Goldberg","year":"2000","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1167\/iovs.15-18500","article-title":"Agi Workshop Participants. Report on the National Eye Institute Audacious Goals Initiative: Regenerating the Optic Nerve","volume":"57","author":"Goldberg","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","unstructured":"Buratto, L. (2011). L\u2019occhio, le Sue Malattie e le Sue Cure, Springer Science & Business Media."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Adornetto, A., Rombol\u00e0, L., Morrone, L.A., Nucci, C., Corasaniti, M.T., Bagetta, G., and Russo, R. (2020). Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma. Nutrients, 16.","DOI":"10.3390\/nu12103158"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1208\/s12249-020-01836-4","article-title":"Nanodelivery of Resveratrol-Loaded PLGA Nanopar-ticles for Age-Related Macular Degeneration","volume":"21","author":"Bhatt","year":"2020","journal-title":"AAPS Pharm. Sci. Tech."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1038\/nprot.2016.065","article-title":"Isolation, culture and characterization of primary mouse RPE cells","volume":"11","author":"Garland","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"894368","DOI":"10.1155\/2014\/894368","article-title":"Culture and characterization of microglia from the adult murine retina","volume":"2014","author":"Devarajan","year":"2014","journal-title":"Sci. World J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1177\/026119291604400608","article-title":"The Novel Induction of Retinal Ganglion Cell Apoptosis in Porcine Organ Culture by NMDA\u2014An Opportunity for the Replacement of Animals in Experiment","volume":"44","author":"Kuehn","year":"2016","journal-title":"Altern. Lab. Anim."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1177\/026119291704500105","article-title":"A novel porcine ex vivo retina culture model for oxidative stress induced by H2O2","volume":"45","author":"Hurst","year":"2017","journal-title":"Altern. Lab. Anim."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1002\/jcp.22532","article-title":"Modulation of oxidative stress responses in the human retinal pigment epithelium following treatment with vitamin C","volume":"226","author":"Yin","year":"2011","journal-title":"J. Cell Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.redox.2018.10.004","article-title":"Ascorbic acid metabolites are involved in intraocular pressure control in the general population","volume":"20","author":"Hysi","year":"2018","journal-title":"Redox Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ramdas, W.D., Schouten, J.S.A.G., and Webers, C.A.B. (2018). The Effect of Vitamins on Glaucoma: A Systematic Review and Meta-Analysis. Nutrients, 16.","DOI":"10.3390\/nu10030359"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/j.1475-1313.2004.00218.x","article-title":"An ideal ocular nutritional supplement?","volume":"24","author":"Bartlett","year":"2004","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_34","first-page":"438","article-title":"Association of severity of primary open-angle glaucoma with serum vitamin D levels in patients of African descent","volume":"25","author":"Ayyagari","year":"2019","journal-title":"Mol. Vis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1080\/10408398.2014.893504","article-title":"Modulatory effects of 1,25-dihydroxyvitamin D3 on eye disorders: A critical review","volume":"57","author":"Buomprisco","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Abouzeid, H., and Samer, C.F. (2020). Vitamin D and Glaucoma: A Critical Review of the Literature. J. Ophthalmol.","DOI":"10.1155\/2020\/8071280"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.lfs.2016.05.006","article-title":"Lycopene inhibits ICAM-1 expression and NF-\u03baB activation by Nrf2-regulated cell redox state in human retinal pigment epithelial cells","volume":"155","author":"Yang","year":"2016","journal-title":"Life Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/aje\/kwg167","article-title":"Antioxidant intake and primary open-angle glaucoma: A prospective study","volume":"15","author":"Kang","year":"2003","journal-title":"Am. J. Epidemiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1089\/jop.2012.0198","article-title":"Black currant anthocyanins normalized abnormal levels of serum concentrations of endothelin-1 in patients with glaucoma","volume":"29","author":"Yoshida","year":"2013","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1159\/000335961","article-title":"Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma","volume":"228","author":"Ohguro","year":"2012","journal-title":"Opthalmologica"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Nomi, Y., Iwasaki-Kurashige, K., and Matsumoto, H. (2019). Therapeutic Effects of Anthocyanins for Vision and Eye Health. Molecules, 24.","DOI":"10.3390\/molecules24183311"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.fitote.2010.09.007","article-title":"Therapeutic orchids: Traditional uses and recent advances- an overview","volume":"82","author":"Hossain","year":"2011","journal-title":"Fitoterapia"},{"key":"ref_43","first-page":"1483","article-title":"Gastrodin protects retinal ganglion cells through inhibiting microglial-mediated neuroinflammation in an acute ocular hypertension model","volume":"10","author":"Wang","year":"2017","journal-title":"Int. J. Ophthalmol."},{"key":"ref_44","first-page":"7774","article-title":"Gastrodin inhibits high glucose induced human retinal endothelial cell apoptosis by regulating the SIRT1\/TLR4\/NF \u03baBp65 signaling pathway","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.brainres.2019.04.025","article-title":"Gastrodin attenuates proliferation and inflammatory responses in activated microglia through Wnt\/\u03b2-catenin signaling pathway","volume":"15","author":"Yao","year":"2019","journal-title":"Brain Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.1038\/s41598-020-61848-9","article-title":"Time course of bilateral microglial activation in a mouse model of laser-induced glaucoma","volume":"10","author":"Rojas","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Park, Y.H., Snook, J.D., Zhuang, I., Shen, G., and Frankfort, B.J. (2020). Optimized culture of retinal ganglion cells and amacrine cells from adult mice. PLoS ONE, 15.","DOI":"10.1101\/2020.06.16.155069"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1167\/iovs.17-22406","article-title":"Culture Systems of Dissociated Mouse and Human Pluripotent Stem Cell-Derived Retinal Ganglion Cells Purified by Two-Step Immunopanning","volume":"59","author":"Kobayashi","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.neuroscience.2008.08.036","article-title":"Elevated pressure triggers a physiological release of ATP from the retina: Possible role for pannexin hemichannels","volume":"157","author":"Reigada","year":"2008","journal-title":"Neuroscience"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.exer.2011.06.020","article-title":"Sustained elevation of extracellular ATP in aqueous humor from humans with primary chronic angle-closure glaucoma","volume":"93","author":"Li","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"931","DOI":"10.3389\/fnins.2019.00931","article-title":"Immune Mediated Degeneration and Possible Protection in Glaucoma","volume":"2","author":"Tsai","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"692609","DOI":"10.1155\/2012\/692609","article-title":"Animal models of glaucoma","volume":"2012","author":"Bouhenni","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1167\/iovs.13-13019","article-title":"Characterization of vitamin D production by human ocular barrier cells","volume":"55","author":"Alsalem","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Anderson, R.E., Hollyfield, J.G., and LaVail, M.M. (2010). Retinal Degeneration Clinical and Laboratory Applications, Springer.","DOI":"10.1007\/978-1-4419-1399-9"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Molinari, C., Morsanuto, V., Ruga, S., Notte, F., Farghali, M., Galla, R., and Uberti, F. (2020). The Role of BDNF on Aging-Modulation Markers. Brain Sci., 10.","DOI":"10.3390\/brainsci10050285"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1089\/wound.2017.0766","article-title":"Highly Diluted Acetylcholine Promotes Wound Repair in an In Vivo Model","volume":"7","author":"Uberti","year":"2018","journal-title":"Adv. Wound Care"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"47912","DOI":"10.1074\/jbc.M409035200","article-title":"Basic fibroblast growth factor-induced cell death is effected through sustained activation of p38MAPK and up-regulation of the death receptor p75NTR","volume":"279","author":"Williamson","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13048-017-0357-9","article-title":"Biological effects of combined resveratrol and vitamin D3 on ovarian tissue","volume":"10","author":"Uberti","year":"2017","journal-title":"J. Ovarian Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jep.2016.09.005","article-title":"Pereskia aculeata Miller leaves accelerate excisional wound healing in mice","volume":"194","author":"Pinto","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.ophtha.2017.02.024","article-title":"Quality of life and functional vision in children with glaucoma","volume":"124","author":"Tailor","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_61","first-page":"141","article-title":"Natural therapies for ocular disorders, part two: Cataracts and glaucoma","volume":"6","author":"Head","year":"2001","journal-title":"Altern. Med. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.exer.2016.12.005","article-title":"The Lasker\/IRRF Initiative on Astrocytes and Glaucomatous Neurodegeneration Participants. Neuroprotection for Glaucoma: Requirements for Clinical Translation","volume":"157","author":"Levin","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_63","first-page":"S11","article-title":"History of neuroprotection and rationale as a therapy for glaucoma","volume":"14","author":"Levin","year":"2012","journal-title":"Am. J. Manag. Care"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11095-019-2588-5","article-title":"Translational Preclinical Pharmacologic Disease Models for Ophthalmic Drug Development","volume":"36","author":"Shah","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1159\/000448480","article-title":"Modeling Human Glaucoma: Lessons from the in vitro Models","volume":"57","author":"Aires","year":"2017","journal-title":"Ophthalmic Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Evangelho, K., Mastronardi, C.A., and de-la-Torre, A. (2019). Experimental Models of Glaucoma: A Powerful Translational Tool for the Future Development of New Therapies for Glaucoma in Humans-A Review of the Literature. Medicina, 55.","DOI":"10.3390\/medicina55060280"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"573775","DOI":"10.3389\/fbioe.2020.573775","article-title":"Design and Validation of a Human Brain Endothelial Microvessel-on-a-Chip Open Microfluidic Model Enabling Advanced Optical Imaging","volume":"8","author":"Salman","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1111\/brv.12626","article-title":"Modelling neurodegenerative diseases with 3D brain organoids","volume":"95","author":"Chang","year":"2020","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_69","first-page":"2190","article-title":"Neuroprotective effects of cannabidiol in endotoxin-induced uveitis: Critical role of p38 MAPK activation","volume":"14","author":"Tang","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"281214","DOI":"10.1155\/2015\/281214","article-title":"Experimentally induced mammalian models of glaucoma","volume":"2015","author":"Ishikawa","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.exer.2010.08.005","article-title":"Pathophysiology of human glaucomatous optic nerve damage: Insights from rodent models of glaucoma","volume":"93","author":"Morrison","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1167\/iovs.07-1601","article-title":"Development and characterization of an adult retinal explant organotypic tissue culture system as an in vitro intraocular stem cell transplantation model","volume":"49","author":"Johnson","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-62703-080-9_7","article-title":"N-methyl-D-aspartate (NMDA)-mediated excitotoxic damage: A mouse model of acute retinal ganglion cell damage","volume":"935","author":"Seitz","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/0261192919840092","article-title":"Retinal Organ Cultures as Alternative Research Models","volume":"47","author":"Schnichels","year":"2019","journal-title":"Altern. Lab. Anim."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Dom\u00e8nech, E.B., and Marfany, G. (2020). The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies. Antioxidants, 9.","DOI":"10.3390\/antiox9040347"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.preteyeres.2006.07.003","article-title":"Oxidative stress in glaucomatous neurodegeneration: Mechanisms and consequences","volume":"25","author":"Tezel","year":"2006","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_77","first-page":"3176","article-title":"Differential susceptibility of retinal ganglion cells to reactive oxygen species","volume":"41","author":"Kortuem","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2817252","DOI":"10.1155\/2017\/2817252","article-title":"Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis","volume":"2017","author":"Kimura","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"238","DOI":"10.2174\/138620708783877753","article-title":"High throughput screening for neurodegeneration and complex disease phenotypes","volume":"11","author":"Varma","year":"2008","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Aldewachi, H., Al-Zidan, R.N., Conner, M.T., and Salman, M.M. (2021). High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases. 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