Single-Cell RNA Sequencing Enhances Precision in Diagnosing and Treating Corneal Blindness

Precision medicine is revolutionizing the treatment of corneal blindness by tailoring interventions to individual genetic makeups. Dr. Gink Yang, a CERA Research Fellow, is at the forefront of this transformation, particularly in the diagnosis and management of Fuchs' endothelial corneal dystrophy (search)Search disease (FECD (search)Search disease). His work leverages single-cell RNA sequencing to provide targeted treatments based on a patient's unique genetic profile.

Advancing FECD Diagnosis with RNA Sequencing

FECD (search)Search disease affects the cornea, leading to fluid buildup and blurred vision due to the gradual death of corneal cells. Affecting 1 in 25 Australians over 40, it is the most common reason for corneal transplants in developed nations. Traditional diagnosis relies on clinical observations like visual acuity and corneal thickness, which Dr. Yang notes, may not always provide a definitive assessment of tissue damage. Single-cell RNA sequencing offers a more precise approach by examining gene expression in individual corneal cells, providing detailed insights into disease progression.

"This technology transforms FECD (search)Search disease diagnosis. It goes beyond observation and empirical evidence - it's an informed approach," says Dr. Yang.

Guiding Treatment Decisions: DWEK vs. Transplant

Ophthalmologists face the challenge of balancing the benefits and risks of corneal transplants, including potential complications and donor tissue availability. Descemet stripping without endothelial keratoplasty (DWEK) is a newer procedure that allows the eye to heal itself by removing damaged cells. Single-cell RNA sequencing can help clinicians determine which patients are better candidates for DWEK versus a full transplant.

"Single-cell RNA sequencing can show, for example, that 80 per cent of the cells in a person's cornea are expressing genes that will lead to the disease. In this case, a transplant is likely the best option," explains Dr. Yang. "Or the data may show that only 20 per cent of the cells are expressing these devastating gene signatures, meaning 80 per cent of the cells are healthy. So a clinician may opt for DWEK."

Clinical Trials and Future Applications

Associate Professor Elaine Chong and Dr. Elsie Chan are conducting a clinical trial at CERA to assess DWEK's suitability in FECD (search)Search disease patients who would typically receive a corneal transplant. While their trial does not currently use single-cell RNA sequencing for patient selection, Associate Professor Chong recognizes its potential.

"The success rate of DWEK in the published literature varies from 70-95 per cent, but patients that were included in these studies were extremely variable," says Associate Professor Chong. "That's why Dr Yang's study is important as it can help us identify who might be the better candidates for this procedure."

Despite its promise, single-cell RNA sequencing requires regulatory approval and faces cost barriers. However, Dr. Yang is optimistic about its future, noting the significant decrease in RNA sequencing costs over recent years. He envisions its potential use in clinics at a fraction of the current cost within the next five years.

International Recognition and Collaboration

Dr. Yang's work has garnered international attention, with a recent Travel Award from Mass Eye and Ear (Harvard University) to present his research at their 2024 biennial conference in Lisbon. His research is supported by Professor Ula Jurkunas from Harvard, a leading expert in FECD (search)Search disease.

"It's all about mitigating the risk of patient suffering. If a patient needs a transplant, we want to make sure the person absolutely needs it. If the person doesn't need it, let's allow the body to regenerate," Dr. Yang concludes, emphasizing the importance of precision in medical decision-making.