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Protein Wnt-a5: a potential cure for diabetic eye disease

A study from the Cedars-Sinai Medical Center in Los Angeles, US, has provided new understanding into the eye deterioration processes of people affected by diabetes, paving the way for new treatments.

Recent research by the Cedars-Sinai Medical Center in Los Angeles examined diabetic eye disease, identifying for the first time the specific damage inflicted to the cornea by diabetes, as well as three potential therapeutic approaches to treat them.

Alexander Ljubimov, PhD, director of the Eye Program at Cedars-Sinai’s Board of Governors Regenerative Medicine Institute and senior author of the paper, emphasized how their research was pivotal in discovering that diabetes is responsible for specific DNA modifications, not by affecting gene sequence but by altering gene expression, a process which is known as epigenetic alteration.

Nearly 5% percent of the Italian population suffers from diabetes, whereas this ratio reaches a staggering 11% in the US. Even though diabetes is a widespread disease, as of today, most treatments mainly focus on increasing glucose tolerance, or supplying insulin to the body, ignoring molecular or cellular changes.

The Cedars-Sinai study also uncovered the pivotal role of the Wnt-a5 signalling protein, which is responsible for corneal wound healing and the function of stem cells.

According to Ruchi Shah, a scientist in Ljubimov’s lab and the study’s first author, understanding of this novel epigenetically regulated wound-healing mechanism could lead to therapeutic treatments that, if effective, could help diabetic patients avoid further long-term ocular health issues.”

A significant 70% of Diabetic patients suffer from problems affecting the cornea, a transparent membrane covering the outer surface of the eye. In patients with advanced diabetes, ocular wounds heal more slowly following injury or surgery, and corneal stem cells become dysfunctional.

In order to verify their hypothesis on epigenetic changes, researchers compared cells from the corneas of six diabetic patients with those of five healthy donors.

The comparison revealed that cells from diabetic patients not only showed a repression of the protein product of the WNT5A gene, but also an increase in microRNA.

Researchers then tested three different treatments aimed at normalising the Wnt-5a protein expression on corneal cell and corneal organ cultures.

All three tested approaches had a positive impact on stem cell marker production and tissue regeneration. After completing the evaluation of the positive outcomes of their study, the Cedars-Sinai team of researchers intend to continue analysing their data to improve currently available treatments.

Sources:

Ophthalmology Times

Springer Link

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