*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.