Highlights

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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References

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

Xinyi Su graduated with MB BChir PhD from University of Cambridge, UK. Currently, she balances her time as Acting Executive Director of the Institute of Molecular and Cell Biology (IMCB) whilst practising as Senior Consultant Vitreo-Retinal Surgeon (NUH). Su is also the Research Director at the Department of Ophthalmology (NUS), and Clinician-Scientist at SERI. Her research focuses on harnessing biomaterial, regenerative stem-cell and nucleic acid technologies for the treatment of retinal degenerative disease. Her work has been published in Nature Biomedical Engineering, Nature Communications, Lancet Global Health, PNAS and Advanced Materials. With a career total of > S$25 million in competitive research grants, Su is the recipient of multiple awards including the APAO Young Ophthalmologist Award (2019), APVRS LDP Gold Award (2020), Ten Outstanding Young Persons of Singapore Award (2021), Susan Lim Outstanding Stem Cell Young Investigator Award (2022) and NMRC Clinician Scientist Award (2022). In 2022, she was accepted into the prestigious international membership of The Macular Society. Passionate about clinical translation, Su holds several patents and co-founded Vitreogel Innovations, focused on developing next-gen vitreous substitutes. Beyond research, Su is committed to talent development. She has mentored numerous clinician scientists as Deputy Director of the Clinician-Scientist Academy (NUHS).

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