Retinal drusen in patients with chronic myeloproliferative blood cancers are associated with an increased proportion of senescent T cells and signs of an aging immune system

Abstract

The cause of age-related macular degeneration (AMD) is unknown, but evidence indicates that both innate and adaptive immunity play a role in the pathogenesis. Our recent work has investigated AMD in patients with myeloproliferative neoplasms (MPNs) since they have increased drusen and AMD prevalence. We have previously found increased levels of chronic low-grade inflammation (CLI) in MPN patients with drusen (MPNd) compared to MPN patients with normal retinas (MPNn). CLI and AMD are both associated with aging, and we, therefore, wanted to study immunosenescence markers in MPNd, MPNn, and AMD. The purpose was to identify differences between MPNd and MPNn, which might reveal novel information relevant to drusen pathophysiology and thereby the AMD pathogenesis. Our results suggest that MPNd have a T cell differentiation profile resembling AMD and more effector memory T cells than MPNn. The senescence-associated-secretory-phenotype (SASP) is associated with effector T cells. SASP is thought to play a role in driving CLI seen with advancing age. Senescent cells with SASP may damage healthy tissue, including the eye tissues affected in AMD. The finding of increased effector cells in MPNd could implicate a role for adaptive immunity and senescent T cells together with increased CLI in drusen pathophysiology.

Busulfan Treatment for Myeloproliferative Disease may Reduce Injection Burden in Vascular Endothelial Growth Factor-Driven Retinopathy

“…Given the known relationship between systemic VEGF levels and JAK2 mutated MPNs, 2 we hypothesize that these patients had elevated systemic VEGF levels due to their underlying cancer with high JAK2 mutation burden, which could have contributed to more severe VEGF-driven retinal disease. In fact, patients with MPNs have a well-described increased risk of age-related macular degeneration, which is associated with higher JAK2V617F allele burden, 8 , 9 and Bak et al described a 1.4-fold increased risk of neovascular age-related macular degeneration in patients with MPNs. 10 …”

Lower CXCR3 expression in both patients with neovascular AMD and advanced stages of chronic myeloproliferative blood cancers

“…The participants consisted of 30 patients with nAMD, 30 iAMD (Beckmann Classification) [ 2 ], and 63 MPNs (WHO2016 criteria) [ 22 ]; of those 35 MPNs with early or intermediate AMD (MPNd) and 28 with normal retinas (MPNn). Inclusion was done between July 2018 and November 2020 [ 23 , 24 ]. Exclusion criteria were patients having other concurrent cancer, inflammatory- or autoimmune diseases.…”

“…Data statistics were done with RStudio v.4.1.1. We based our power calculation on prior comparable immunologic studies of these patients, resulting in a sample size of a minimum of 26 in each group [ 23 , 24 ].…”

Retinal Manifestations in Patients with Myeloproliferative Disorders

“…MPH' de daha erken yaşta ve daha sık YBMD gelişmesinde her iki hastalıkta da görülen düşük dereceli inflamasyon, regülasyonu bozulmuş komplement sistemi ve azalmış CXCR3 ekspresyonunun etkili olabileceğini düşünmüşlerdir. [35][36][37][38]…”