The way Diabetes Hinders the Healing Process in the Eye

Researchers have presented fresh insights into the mechanism by which diabetes affects the healing of eye wounds. For the first time, they have identified two related disease-associated changes to the cornea.

Investigators at Cedars-Sinai have gained fresh insights into how diabetes hampers wound healing in the eye. For the first time, they have identified two disease-associated changes in the cornea. Published in the journal Diabetologia, the study also revealed three therapeutic pathways capable of reversing these changes and partially restoring wound-healing function to the cornea. This discovery may pave the way for new diabetes treatments.

Insights from Dr. Alexander Ljubimov’s Research

Dr. Alexander Ljubimov, the director of the Eye Program at Cedars-Sinai’s Board of Governors Regenerative Medicine Institute and the senior author of the paper, explained that diabetes leads to extensive cellular changes, involving specific DNA modifications known as epigenetic alterations, which alter gene expression.

With over 37 million people in the United States having diabetes, it’s crucial to find treatments that address not only symptoms but also the underlying molecular and cellular changes associated with the disease’s complications.

The research also highlighted the significant role of Wnt-5a, a secreted signaling protein responsible for corneal wound healing and the functioning of stem cells. While diabetic eye disease often focuses on the retina, the cornea, which is the transparent, protective exterior surface of the eye, is affected in up to 70% of diabetes patients.

In advanced diabetes, corneal stem cells become dysfunctional, leading to slower and less complete healing following injuries or procedures like cataract surgery and laser treatment for diabetic retinopathy.

Understanding these novel epigenetically regulated wound-healing mechanisms could hold promise for developing therapeutic treatments to prevent long-term ocular health issues in patients.

Comparing Cellular Differences Between Diabetic and Healthy Individuals

In this study, researchers aimed to identify epigenetic changes, which are modifications introduced later in life and not hard-wired into the genome from birth. In fact, to achieve this, Dr. Ljubimov and his team compared corneal cells from six diabetic patients with those from five healthy donors. They observed that in diabetic corneas, the protein product of the WNT5A gene was suppressed, and there was an increase in the microRNA that inhibits WNT5A.

Targeting Wnt-5a Protein Expression in Corneal Wounds

However, to investigate potential therapeutic approaches, the scientists induced wounds in cultured corneal cells and corneal organ cultures. They tested three interventions to normalize Wnt-5a protein expression: direct addition of the Wnt-5a protein, the use of a DNA methylation inhibitor (originally approved for cancer treatment), and a novel gene therapy approach using a nanoscale compound to target microRNA levels. The team developed the nanoscale compound as an alternative to a toxic viral gene therapy that had adverse effects on stem cells.

All three therapeutic methods showed promising results in the diabetic samples, stimulating the production of stem cell markers and improving tissue regeneration, ultimately accelerating wound healing.

Dr. Clive Svendsen, study co-author, pointed out that reversing epigenetic effects with novel therapies could not only improve corneal function but also hold significance for other diabetic complications, moving the field forward in terms of treatment options.

Analyzing Mechanisms of WNT5A and Exploring Combination Therapy for Enhanced Wound Healing

Moving forward, the investigators will continue analyzing their data to gain a better understanding of the mechanisms of WNT5A and other genes related to wound healing. They are also exploring the potential of a combination therapy to target both microRNA and DNA methylation, aiming to more effectively normalize wound healing by increasing Wnt-5a protein.

To conclude, the ultimate goal of their research is to develop topical, sustained-release drugs for corneal wound healing. These FDA-approved drugs could be easily applied and offer promising avenues for effective future therapies.

Read the original article on: Science Daily

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