Scientists bring to life ‘a sight for sore eyes’

Doctors in Star Trek are the kind of doctors we all want to have – the ones that
can heal cuts and burns instantly with a ray gun. Scientifically speaking, we still
have some way to go before such a gun becomes realistically conceivable, even as
we continue to learn about the different tissues in our bodies.
 
One such specialised tissue is the cornea or sclera of the eye, which, as the outermost layer, functions to protect the eye from infection but also maintains the intraocular pressure.
 
For those of us who don’t remember our high school biology, the eye is quite literally
an inflated ball within which a certain pressure needs to be maintained so that the
retina at the back of the ball is constantly pushed against, and attached to, the
wall. Full-thickness eye injuries, also known as open globe injuries, through the
cornea or sclera are complicated and require immediate treatment to prevent
deterioration or even loss of vision, which tends to happen as the intraocular
pressure drops and causes retinal detachment. Currently, such eye surgeries are
dealt with by stitching the remaining margins from the wound together and
allowing the tissue to heal itself.
 
This surgery requires a high level of expertise, specific equipment and a significant amount of time. However, in some cases, such materials and expertise are not available. Imagine war fronts, where eye injuries are common due to flying shrapnel. Or perhaps, there are other, more severe and threatening injuries that need to be dealt with first. For situations like these, some sort of temporary wound sealant is required for the eye to prevent its deflation.

Enter a group of scientists led by PhD student Niki Bayat at the University of
Southern California, who have invented such a band-aid for eye injuries in the form
of a smart hydrogel. If you have ever used a sealant, or even glue, then just
imagine that, contained in a little dispenser, as a plaster for your eyes. The great
thing, however, is that it is not an adhesive, meaning that after it has done its job
of holding the wound margins together, it can be easily removed without causing
any damage to the surrounding tissue, allowing for complete surgery procedure.

The key to all this? It is thermoresponsive, meaning it has different properties at
different temperatures. In this case, the hydrogel is liquid at temperatures lower
than average body temperature and is solid at body temperature or higher. Being
liquid at lower temperatures means that it can be stored and injected as a liquid
with ease, and washed out as a liquid with cold water once surgery is possible. It’s
as easy as that. It is also significantly less irritating than temporary stitches, which
otherwise cause patients to rub their eyes, slowing the progress of healing and
increasing the chances of infection.
 
This is because the sealant shape-fills according to the wound which also makes it much more effective at maintaining the intraocular pressure (preventing deflation), as shown by the scientist that performed such surgeries on rabbits to test the ease and effectiveness of the gel. By using the hydrogel through a custom, temperature controlled syringe, they saw that the intraocular pressure returned to almost normal levels over the course of 72 hours, with improvement already being shown 12 hours after injection. This was following a greater than 80% decrease in pressure from the normal due to the injury. This recovery is almost twice the magnitude of no treatment, in other words, a 100% improvement. Meanwhile, it was also shown that it was strong enough as a sealant to maintain an intraocular pressure five times greater than the physiological range for over 30 days – much longer than its intended use.

This magic hydrogel is made with a polymer that has been known to scientists for
60 years, called N-isopropylacrylamide. Interestingly, this material’s first use was
patented as a rodent repellent by Jr Newton H Shearer (1), and it wasn’t until 1968
that its thermoresponsive properties in aqueous solutions were discovered by M.
Heskins and J.E. Guillet (2). About half a century down the line, the scientists from
the University of Southern California ran multiple tests with different formulations
of this polymer with another polymer called butylacrylate to adjust the
thermoresponsive range to be perfect for use in humans in order to finally create
the smart hydrogel. According to the National Institute for Occupational Safety and
Health (NIOSH), butylacrylate is hazardous to humans on its own due to its
volatility, and ironically one of the first symptoms from exposure is corneal
irritation and necrosis (3). But in the hydrogel, as a copolymer, it has been shown
to be safe; the rabbits that the scientists tested the gel on showed no damage,
neurotoxicity or significant levels of inflammatory response (similar to what would
be seen following any injury) over the course of 30 days of exposure.

“The moldability, persistence in form, and sufficient toughness to withstand
intraocular pressure”, as the paper states, make this hydrogel optimal for its
application and give it the potential to be further tweaked to deal with other tissue
injuries and have other applications. In fact, Niki Bayat has co-founded the
company AesculaTech, which has been working on a similar polymer that can be
used to deliver perfect and timely dosage of glaucoma drugs to patients through
the insertion of the polymer into the tear ducts of patients (4). Of course, both
these inventions still need to be FDA-approved, which is time-consuming.
However, Niki is determined – motivated by seeing her own father struggle through
losing vision as a glaucoma patient, she knows the importance of such products.
According to the Royal National Institute of Blind People, in 2016, there were an
estimated 2 million people in the UK living with sight loss. Meanwhile, the direct
and indirect costs linked to eye health was over £29 billion for the NHS (5). Both
these figures are crippling. New inventions like these offer a new hope and promise
of being effective in preventing sight loss, contributing to better quality of life for
individuals and reduced costs for nations. It doesn’t get any more of ‘a sight for
sore eyes’ than that.
 
Written by Arushi Agrawal

Paper:
Bayat N, Zhang Y, Falabella P, Menefee R, Whalen JJ, Humayun MS, et al. A
reversible thermoresponsive sealant for temporary closure of ocular trauma. Sci
Transl Med. 2017 Dec 6;9(419):eaan3879.

References:

1. Shearer Jr. NH, Coover HW. US2790744 – Amide rodent repellent
compositions. US Patent Office; 2790744, 1954.

2. Heskins M, Guillet JE. Solution Properties of Poly(N-isopropylacrylamide). J
Macromol Sci Part A – Chem. 1968 Dec 1;2(8):1441–55.

3. The National Institute for Occupational Safety and Health. CDC – NIOSH
1988 OSHA PEL Project Documentation: n-BUTYL ACRYLATE [Internet].
1988 [cited 2018 Jan 14]. Available from:
https://www.cdc.gov/niosh/pel88/141-32.html

4. Bayat N. aesculatech [Internet]. 2015 [cited 2018 Jan 14]. Available from:
https://www.aesculatech.io/

5. Simkiss P, Dennison C, Edwards E, Edwards R, Flynn K, Lee H, et al. The
State of the Nation Eye Health 2016. 2016;