The
aqueous outflow passages consist of the conventional and the unconventional
pathways. The former route is through the trabecular meshwork and Schlemm’s
canal, while in the latter approximately 15% of the aqueous flows out through
the ciliary muscle, supraciliary muscle and suprachoroidal space.
The
unconventional outflow pathways itself includes two routes, the uveoscleral
pathway and the uveovortex pathway. The uveoscleral pathway indicates drainage
of aqueous humor through the sclera, which is finally absorbed by the orbital
blood vessels, while in the uveovortex pathway aqueous humor enters the choroid
and drains through the vortex vein.
The
suprachoroidal space (SCS) is the potential space between the choroid and the
sclera, which forms part of the uveovortex pathway in the circulation of
aqueous humor.
Recently,
SCS injection of commercial hyaluronic acid (HA) hydrogel and modified HA
hydrogel has been reported to reduce IOP for a period of time in rabbits.
However, the HA hydrogel exhibited a short retention time in the SCS, and there
was also minor hemorrhage and fibrosis at the injection site. In vivo injection
of collagenase could also expand the SCS of rabbit eyes, which was usually well
tolerated, but the duration of IOP reduction was also not long enough.
In
recent years, zwitterionic hydrogels have been applied in a wide range of
biomedical engineering fields. These zwitterionic hydrogels have excellent
antifouling ability to resist adsorption and adhesion of proteins and cells,
thus mitigating inflammation and the formation of fibrosis after implantation.
In
an experiment reported by Hao and colleagues from Tianjin Key Laboratory of
Retinal Functions and Diseases, polycarboxybetaine (PCB-OAA) macromonomer,
which could in situ form a hydrogel in vitreous cavity by crosslinking with
dithiothreitol (DTT) through the Michael addition reaction was injected into
the SCS.
About
100 μL of HA (which acted as control) and PCB-OAA hydrogels were injected into
the SCS, using a microneedle of 1.5 mm length to avoid damage to the retina and
other ocular tissues.
Before
the operation, the averaged IOP value for each group was 12 ± 0.5 mmHg by
continuous measurement for 1 week. At 3 days post-surgery it was observed that
the HA hydrogel group and PCB-OAA hydrogel group both showed a IOP reduction of
approximately 4 mmHg compared with the normal group, which was at the lowest
level, proving that HA and PCB-OAA hydrogels were successfully injected into
the SCS space. In the following 4 weeks, the IOP of the HA group increased
steadily over time and approached the normal level. However, in the PCB-OAA
hydrogel group, IOP maintained a lower value than HA group and still showed
about 2 mmHg reduction at 28 days post-operation. Then at 8 weeks, IOP in the
PCB-OAA hydrogel group increased to a normal level. These results showed that
injecting PCB-OAA hydrogels into SCS could reduce IOP for approximate 8 weeks,
superior to the performance of HA hydrogel.
Ultrasound
biomicroscopy (UBM) was performed during the study period to assess the SCS. The
largest expanded SCS was observed both in the HA and PCB-OAA hydrogel group 3
days post-operation, which was coincident with the highest IOP reduction (4
mmHg). Additionally, it was worth noting that the SCS space gradually became
smaller during the subsequent 8 weeks.
It
respectively took 4 and 8 weeks for HA and PCB-OAA hydrogel to achieve complete
SCS collapse.
Histopathological
examination following completion of the study showed both HA and PCB-OAA
hydrogel groups had complete retinal structure, indicating that the
suprachoroidal injection had no negative effect on the morphology of the
retina. There was no pathological inflammation and fibrosis around SCS in the
HA and PCB-OAA hydrogel groups compared with the normal group.
 |
| HA INJECTION |
Technologies
such as this polyzwitterion hydrogel can be used in the future to treat ocular
hypertension and glaucoma without high cost or resorting to daily medication or
complicated surgical intervention.
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