In brief

Poly(CEP), a biodegradable polymer, can inhibit aberrant wound healing pathways associated with retinal scarring.

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Polymers: more than meets the eye?

2 Feb 2023

A new polymer gel may offer a drug-free solution to preventing retinal scarring after eye surgery.

While any surgery has risks, some have potential complications that can undo their intended results. In patients recovering from retinal reattachment surgery, uncontrolled inflammation and overactive tissue regeneration can culminate in scarring in the eye, often leading—ironically—to vision loss.

Retinal scarring, also known as proliferative vitreoretinopathy (PVR), is notoriously difficult to treat due to its complexity. “Although many treatments targeting PVR’s many pathways have been explored, there is no effective pharmacologic agent to date for the prevention or reversal of the condition,” explained Xinyi Su, a Senior Principal Investigator at A*STAR’s Institute of Molecular and Cell Biology (IMCB).

Taking a different approach to the problem, Su teamed up with researchers at the Institute of Materials Research and Engineering (IMRE) to explore the possibility of using polymeric hydrogels to modulate the out-of-control healing pathways that lead to PVR.

The team developed a synthetic polymer using a mixture of biomaterials typically used as drug carriers. The new thermosensitive material, called poly(CEP), has a gel-like consistency and can gradually degrade once injected into the eye, where it then slowly releases anti-inflammatory polymer molecules.

According to Su, this slow release is what will make a difference for PVR patients. “PVR prevention requires sustained inhibition over a long period with the concurrent inhibition of the multiple initiating factors,” she explained.

When the researchers tested poly(CEP)’s potential in a rabbit model of PVR and cell cultures, they found that retinal cells in the eye absorbed the polymer over time. This triggered the activation of a signalling pathway that blocks or prevents scar formation.

Poly(CEP) holds tremendous promise to boost postoperative healing, say the researchers. Not only can the clear polymer function as a vitreous substitute to help support the retina, but it can also simultaneously prevent scarring without the need for more medication. Beyond the eye, the polymer could also prevent scarring in other areas such as the joints or the skin.

Together, these breakthrough results change the view that synthetic polymers act only as inert carriers. Instead, Su and her team have demonstrated that polymers alone can change the way cells behave and function.

“This provides an unprecedented opportunity to tailor specific cellular processes by modifying polymer properties,” said Su, adding that ongoing research efforts are focused on customising polymer 'recipes' to evoke specific healing responses.

The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology (IMCB), Institute of Materials Research and Engineering (IMRE) and Bioinformatics Institute (BII).

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Parikh, B.H., Liu, Z., Blakeley, P., Lin, Q., Singh, M., et al. A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway.  Nature Communications 13, 2796 (2022). | article

About the Researcher

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Xinyi Su

Acting Executive Director and Senior Principal Investigator

Institute of Molecular and Cell Biology (IMCB)
Xinyi Su is the Acting Executive Director and Senior Principal Investigator at the Institute of Molecular and Cell Biology (IMCB). She completed her medical and PhD degrees at the University of Cambridge and joined IMCB in 2016. Su practices ophthalmology as a Senior Consultant in Vitreo-retinal surgery at the National University Hospital (NUH), Singapore. She also holds joint appointments as Research Director at the Department of Ophthalmology, National University of Singapore (NUS), and Clinician-Scientist at the Singapore Eye Research Institute (SERI). Su’s research interests focus on harnessing biomaterial, regenerative stem-cell, and nucleic acid technologies for the treatment of age-related retinal degenerative disease. Her research has been published in many top-tier scientific journals and she has obtained a career total of over SGD25 million in competitive research funding. Su is also the recipient of multiple global and national awards, including the Susan Lim Outstanding Stem Cell Young Investigator Award (2022) and National Medical Research Council Clinician Scientist Award (2022).

This article was made for A*STAR Research by Wildtype Media Group