‘Multiomic characterization of ocular graft versus host disease from patient tears’ Dr. Emily Grennan

Annual Grant Scheme 2021

Haematopoietic stem cell transplantation (HSCT) is a potentially curative form of treatment for a wide range of haematological diseases, including lymphoma, leukaemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and myeloproliferative syndromes. However, with the increase survival has come an increase in chronic complications, predominately that of graft versus host disease (GVHD).

Although GVHD can have a multitude of systemic manifestations in affected patients, ocular GVHD is one of the most frequent and long-term complications and is associated with significant morbidity and a marked reduction in quality of life. It can affect all parts of the eye, but occurs primarily on the ocular surface, resulting in dry eye disease (DED) or keratoconjunctivitis sicca. The pathogenesis is complex and incompletely understood. However, it has been observed that DED related GVHD evolves in a similar fashion to that of primary Sjogren’s syndrome, with the destruction and fibrosis of lacrimal glands and conjunctiva, leading to tear film deficiency and instability.

Our preliminary studies have indicated that miR expression is dysregulated at the ocular surface and is involved in the pathogenesis of DED observed in patients with primary Sjogren’s syndrome. In a similar fashion, we hypothesize that epigenetic mechanisms that regulate the interplay between inflammatory cytokine networks, innate immune cells and their mediators are dysregulated in ocular GVHD patients thereby contributing to disease pathology.

Although ocular GVHD is common, currently there are no widely accepted guidelines available for its management, and no suggested regime of treatment that is completely satisfactory. So far, prophylactic treatment strategies for ocular GVHD have yet to be developed and treatment is normally initiated based on symptoms and often after permanent ocular tissue changes and surface damage has occurred.

Web Design and Development by Fusio, Dublin