Cascade of Inflammatory, Fibrotic Processes, and Stress-Induced Senescence in Chronic GVHD-Related Dry Eye Disease

Ocular graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Ocular GVHD affects recipients' visual function and quality of life. Recent advanced research in this area has gradually attracted attention from a wide range of physicians and ophthalmologists. This review highlights the mechanism of immune processes and the molecular mechanism, including several inflammation cascades, pathogenic fibrosis, and stress-induced senescence related to ocular GVHD, in basic spectrum topics in this area. How the disease develops and what kinds of cells participate in ocular GVHD are discussed. Although the classical immune process is a main pathological pathway in this disease, senescence-associated changes in immune cells and stem cells may also drive this disease. The DNA damage response, p16/p21, and the expression of markers associated with the senescence-associated secretory phenotype (SASP) are seen in ocular tissue in GVHD. Macrophages, T cells, and mesenchymal cells from donors or recipients that increasingly infiltrate the ocular surface serve as the source of increased secretion of IL-6, which is a major SASP driver. Agents capable of reversing the changes, including senolytic reagents or those that can suppress the SASP seen in GVHD, provide new potential targets for the treatment of GVHD. Creating innovative therapies for ocular GVHD is necessary to treat this intractable ocular disease.

Automated summary

Ocular graft-versus-host disease is a major complication after allogeneic hematopoietic stem cell transplantation, impacting patients' visual function and quality of life. In addition to the classical immune process, changes in senescent cells and stem cells may also contribute to the disease progression. Innovative therapies targeting the senescence-associated changes in immune cells and the inflammatory processes could provide new potential targets for treating GVHD effectively.