International Frontier: emerging therapy for limbal stem cell deficiency ARVO 2022


Limbal stem cell deficiency (LSCD) is an ocular surface disease caused by the imbalance of corneal epithelial homeostasis caused by the decline of the number or function of limbal stem cells. LSCD patients can develop persistent corneal epithelial defect, chronic inflammation, corneal ulcer, corneal epithelial conjunctivalization and neovascular invasion, and even cause serious visual impairment and even blindness. During the ARVO 2022 conference, international ophthalmology news had the honor to interview Professor Sophie X. Deng, an international ophthalmologist, and shared the current options and research progress of emerging therapies for LSCD.

LSCD emerging therapies and scope of application

In recent decades, significant progress has been made in the internal and external treatment of limbal stem cell deficiency (LSCD) through the combination of innovative pharmacological strategies, surgical techniques, bioengineering and cell therapy. Professor Deng pointed out that the pathophysiology and diagnostic stage of LSCD are the basis for formulating treatment plans. If the pathophysiology process and disease status are not understood, the treatment strategy is likely to be wrong. Professor Deng described the applicable groups of different treatment methods:

Innovative pharmacological strategy: applicable to the situation where stem cells are still left in the eyes.

Surgical technique: stem cell transplantation can directly transfer stem cells. The simple limbal epithelial transplantation (SLET) initiated by Professor Virender Sangwan performs well in most LSCD patients, but it is not suitable for all patients.

Bioengineering: gene therapy is applicable to LSCD patients caused by genetic defects, and the process shall meet the good manufacturing practice (GMP) and safety requirements regulated by the United States.

Cell therapy: after cell culture in vitro, cells are transplanted in combination with surgical technology.

The treatment of LSCD depends on the etiology and the degree of stem cell deficiency. Today's era is the golden age of LSCD therapy exploration, and a new generation of therapy is about to emerge.

Advantages and challenges of Wnt signaling pathway in stem cell therapy

Stem cells are regulated by Wnt signaling pathway/ β- The activation of catenin signaling is a very hot research topic in stem cell therapy and regenerative medicine. However, it should be noted that when Wnt signal is not controlled, it may lead to cancer. Professor Deng believes that the control of Wnt signaling pathway is actually a balance. Due to the difficulty of purification of Wnt molecules, small molecules have to be used. Deng team is cooperating with Professor Jie Zheng, a master of small molecule design, and hopes to change the dose and treatment time through small molecules, which means that Wnt signaling pathway (including standard and non-standard pathways) can be controlled without genetic modification in the future, which can also better promote the development of clinical treatment transformation.