Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment for hematologic malignancy and bone marrow failure disorders. Graft-versus-host disease (GVHD) is a major complication of allo-HSCT and can be distinguished into acute (aGVHD) and chronic (cGVHD) types [1]. cGVHD is characterized by chronic tissue inflammation and fibrosis in cGVHD-susceptible organs, including the eyes, mouth, intestine, and liver [2]. Ocular GVHD, affecting approximately 50% of patients with cGVHD, primarily manifests as keratoconjunctivitis sicca [3].

Meibomian gland dysfunction (MGD), a prevalent ocular surface disorder, is characterized by morphological abnormalities in MGs, inflammatory alterations at the lid margin, terminal duct obstruction, and/or quantitative and qualitative changes in glandular secretion [4,5]. MGD is observed in 45–60% of patients with ocular GVHD [[6], [7], [8]].

It is regarded as an age-associated disease owing to its prevalence in individuals aged >60 years (71.7% prevalence) [9], with a positive correlation between its occurrence and age [10]. Recent studies have also demonstrated the relationship between aging and cGVHD, as advanced age in either recipients or donors is a risk factor for cGVHD development [2,11].

Cellular senescence is the irreversible cell cycle cessation induced in diverse biological and pathological settings including stress due to inflammation and irradiation in the cellular environment [12,13]. These senescent cells discharge inflammatory cytokines and chemokines, constituting the senescence-associated secretory phenotype (SASP) [[14], [15], [16]]. We investigated the relationship between aging and ocular GVHD by focusing on cellular senescence, its corresponding SASP, and the senolytic compound ABT-263 (Navitoclax) [14,15,17]. ABT-263, a senolytic agent, operates through selective inhibition of anti-apoptotic Bcl-2 family proteins. It triggers apoptosis and eliminates senescent cells by activating the pro-apoptotic proteins Bak and Bax [[17], [18], [19], [20]]. We reported the hastening of cellular senescence and SASP in lacrimal glands (LGs) of a cGVHD mouse model involving allogeneic bone marrow transplantation (BMT) of MHC-compatible, miHA-mismatched bone marrow. Notably, the application of ABT-263 mitigates cGVHD severity in LGs [21]. Given the established risk associated with aging and MGD, coupled with the accelerated cellular senescence observed in LGs of the cGVHD mouse model, we posit a potential correlation between cellular senescence and MGD observed in cGVHD. Accordingly, we aimed to elucidate the relationship between cellular senescence and MGD in this cGVHD mouse model, that also exhibits inflammation and MGD in the eyelids [22], using ABT-263.