*Corresponding author: Stefania Vernazza IRCCS, Fondazione G.B. Bietti, Rome, Italy; ISSN: 0976-3031 Research Article EFFECT OF ITRAB SOLUTION ON 3D HUMAN TRABECULAR MESHWORK CULTURE Sergio Claudio Saccà 1 , Stefania Vernazza 2 *, Sara Tirendi 3,4 , Sonia Scarfì 4,5 , Stefano Gandolfi 6 , Alberto Izzotti 3§, and Anna Maria Bassi 3,4§ 1 IRCCS, San Martino General Hospital, Ophthalmology Unit, Genoa, Italy; 2 IRCCS, Fondazione G.B. Bietti, Rome, Italy; 3 Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy; 4 Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), Italy; 5 Department of Earth, Environmental and Life Sciences (DISTAV), University of Genoa, Genoa, Italy; 6 Ophthalmology Unit, Department of Biological, Biotechnological and Translational Sciences, University of Parma, Parma, Italy DOI: http://dx.doi.org/10.24327/ijrsr.2020.1103.5156 ARTICLE INFO ABSTRACT iTRAB , a patented formulation of high-concentration polyphenols, catecholamines and fatty acids, has been reported to exert beneficial effects on 2D models of human trabecular meshwork subjected to chronic oxidative stress. In the present study, we analysed the drivers of daily iTRAB administration in counteracting the effects of chronic oxidative stress (500M H 2 O 2 /day), by using an advanced in vitro model based on 3D- trabecular meshwork cells and bioreactor technology to better mimic the microenvironment of trabecular meshwork. In these experimental conditions, iTRAB treatment effectively prevented the increase in intracellular reactive oxygen species production and reduced the level both of the pro-inflammatory (NF-kB, IL1α, IL6 and TNFα) and the pro-fibrotic (TGFβ) markers and as well as the matrix metalloproteinases. Moreover, iTRAB showed to exert anti-apoptotic effects that were associated with trabecular meshwork viability restoration. These results suggest that the antioxidant effects of iTRAB could play a protective role also towards the impairment of trabecular meshwork tissue in POAG. INTRODUCTION Glaucoma is a complex neurodegenerative disease with several target tissues and a relevant molecular complexity [2] . It is considered as the most common cause of blindness worldwide, which affects more than 70 million people in the world, a figure set to rise in the coming years [1] . Until today, therapeutic approaches have been mainly targeted to counteract this disease by lowering intraocular pressure (IOP) by antihypertensive drugs or surgery, because IOP has been proven to play a critical role in the progressive death of RGC. However, these approaches often fail because they do not offer complete protection towards sight deterioration [3,4] . Hence, there is a growing need to find both new molecular targets and new experimental approaches [5–7] to improve glaucoma knowledge. As known, trabecular meshwork (TM), the tissue responsible for aqueous humor outflow from the anterior chamber of the eye, plays a crucial role in IOP regulation [8,9] . Indeed, in high tension glaucoma, TM is considered the most important tissue of the anterior chamber because it is involved in the first events that lead to glaucoma [8] . TM changes, including its cellularity reduction [4] , accumulation of pro inflammatory cytokine [10] , the loss of ECM turnover [11] and so on, are known to be relevant glaucoma features. In particular, several previous studies reported that oxidative stress (OS) plays a pivotal role in promoting both TM dysfunction and therefore the IOP [10,12–14] . Furthermore, Saccà et al. (2016) hypothesized that the pro- apototic signals, which lead to RGC death, start from the suffering cells of the trabecular meshwork [15] . Hence, TM alterations induce aqueous humor proteome changes [16] that, reaching the posterior segment, take on the functions of apoptosis activators for RGC [15] . Therefore, from a molecular point of view, the anterior segment of the eye, of which TM is Available Online at http://www.recentscientific.com International Journal of Recent Scientific Research International Journal of Recent Scientific Research Vol. 11, Issue, 02 (A), pp. 37675-37682, February, 2020 Copyright © Sergio Claudio Saccà et al, 2020, this is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. DOI: 10.24327/IJRSR CODEN: IJRSFP (USA) Article History: Received 14 th December, 2019 Received in revised form 29 th January, 2020 Accepted 05 th February, 2020 Published online 28 th March, 2020 Key Words: iTRAB , trabecular meshwork, oxidative stress, glaucoma, polyphenols, bioreactors.