- Lower levels of
protein in the eye increases intraocular pressure, leading to glaucoma,
finds a new research
- Injecting an
antibody ABTAA (Ang2-binding and Tie2-activating antibody) in the eye
reduces intraocular pressure and reverse the progression of glaucoma
- The findings
could be a promising therapeutic option for glaucoma
A new mechanism involved
in the development and progression of glaucoma has been identified by a
research team at the Center for Vascular Research, within the Institute for
Basic Science (IBS). The team also found a therapeutic approach to treat
The findings of the
in the Journal of Clinical Investigation
help in the development of new therapies to treat primary open-angle glaucoma
(POAG), which counts for three-quarters of all glaucoma patients.
The Development and
Progression of Glaucoma
Abnormally high pressure
inside the eye is one of the most important risk factors for glaucoma. Aqueous
is a transparent watery fluid which is constantly produced and
drained out from the eye. It transports nutrients and oxygen to the cells and
inflates the eye giving it a roughly spherical shape. But, when the fluid
cannot flow out of the eye chambers freely, an intraocular pressure
increases, which damages
the optic nerve, leading to vision loss.
‘Impairment of Angiopoietin-Tie2 system in the eye’s Schlemm's canal, increases intraocular pressure, leading to glaucoma. An antibody called ABTAA (Ang2-binding and Tie2-activating antibody) was found to reduce intraocular pressure and rejuvenate the eye.’
The mechanism of
elevated resistance to aqueous humor outflow remains unclear. The current
treatments for glaucoma tackle the production and outflow of aqueous humor, but
their outcomes are still poor.
Schlemm's canal is a
component of the eye that plays a key role in draining out the aqueous humor.
collects the aqueous humor and mediates its transfer from the eye chambers. The
endothelial cells on the walls of the Schlemm's canal transfer the fluid from
the inner to the outer side in packages called 'vacuoles.' The shape and number
of the vacuoles reflect the outflow performance. Thus, several giant vacuoles
are expected in the normal outflow process.
Imbalance in Schlemm's
Canal Increases Risk
The research team
explained how imbalances in Schlemm's canal significantly increase the risk of
glaucoma. Angiopoietin-Tie2 is an important regulator for canal functionality.
Angiopoietins Ang1 and Ang2, are proteins important for the growth of new blood
vessels and angiopoietin-Tie2 is a receptor that binds them.
plays a critical role in Schlemm's canal formation.
mutations or the absence of angiopoietin can result in congenital glaucoma.
However, this also plays a role in the development of glaucoma during
The research team
conducted a study on mice to study the development of glaucoma. They found that
adult mice deficient in Tie2 showed an elevated intraocular pressure, retinal
neuronal damage and partial visual impairment.
They also found a
decreased number of giant vacuoles inside Schlemm's canal endothelial cells,
which indicate a poor aqueous humor outflow.
The research team also
investigated how this process occurs in older mice because aging is also a
major risk factor for glaucoma. They found that older mice experience reduced levels
of giant vacuoles, Tie2, Ang1, and Ang2. Other proteins that are connected with
the angiopoietin-Tie2 pathway, like Prox1 were also reduced in older mice.
New Treatment for
The research team tested
if the activation of Tie2 could reverse the condition. They injected
an antibody ABTAA (Ang2-binding and Tie2-activating antibody)
in one eye
of mice, while the other eye of the same mice was the negative control.
After one week of
observation, the research team found that the eye treated ABTAA had
increased levels of Tie2, Prox1 and the number and diameter of giant vacuoles
in the Schlemm's canals also increased when compared to the control eye.
The intraocular pressure
in the eye also decreased after ABTAA was injected into the eyes of mice suffering
from POAG with regressed Schlemm's canals.
The findings indicate
that the antibody ABTAA could be a therapeutic option for treating glaucoma.
of glaucoma treatments is partly due to the poor understanding of the
underlying pathogenesis. We hope that identifying the critical role of the
angiopoietin-Tie2 system in adult Schlemm's canals will bring a significant
boost in the development of therapeutics," said KOH Gou Young, the
corresponding author of the study. "
the second leading cause of irreversible blindness, affecting about 3.5% of the
world population aged 40 to 80.
The two major types of
Facts About Glaucoma
- Early treatment
could help prevent glaucoma
- Anyone could be at risk for glaucoma
- There are no
- People of Asian
descent are at a higher risk for angle closure glaucoma
- People of African
or European origins are at greater risk for primary open angle glaucoma
- The prevalence of
glaucoma in Southern India is 2.6%,
however, 90% of
these cases have never been diagnosed early
glaucoma has reached epidemic proportions in China and some parts of Asia
- Glaucoma is second leading cause of blindness globally - (http://www.who.int/bulletin/volumes/82/11/feature1104/en/index1.html)
- Jaeryung Kim, Dae-Young Park, Hosung Bae, Do Young Park, Dongkyu Kim, Choong-kun Lee, Sukhyun Song, Tae-Young Chung, Dong Hui Lim, Yoshiaki Kubota, Young-Kwon Hong, Yulong He, Hellmut G. Augustin, Guillermo Oliver,and Gou Young Koh1. Impaired Angiopoietin/Tie2 Signaling Compromises Schlemm's Canal Integrity and Induces Glaucoma. Journal of Clinical Investigation (2017). DOI:https://doi.org/10.1172/JCI94668DS1