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.

Charlotte Liisborg,Lasse Kjær,Torben Lykke Sørensen,Vibe Skov,Hans Carl Hasselbalch

doi:10.18632/aging.203803

Charlotte Liisborg, Lasse Kjær + Show 3 more

Open Access

https://doi.org/10.18632/aging.203803

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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.

Highlights

The exact cause of the eye disease age-related macular degeneration (AMD) is unknown, but the most significant risk factor is aging [1]
We detected no difference in JAK2V617F allele burden between the two myeloproliferative neoplasms (MPN) groups (p = 0.088), but it seemed that MPN patients with normal retinas (MPNn) had a lower allele burden of 17% compared to 33% for MPN patients with drusen (MPNd)
We have investigated the immune systems of patients with MPNs because they have an increased prevalence of drusen and late AMD [14]

Summary

Introduction

The exact cause of the eye disease age-related macular degeneration (AMD) is unknown, but the most significant risk factor is aging [1]. A study estimates that nearly 200 million people globally have AMD. These numbers are expected to rise to nearly 300 million by 2040 due to increased life expectancy [2]. AMD is a debilitating disease affecting central visual acuity and complicates everyday activities such as reading, driving, and recognizing faces. There is an urgent need for a better understanding of the condition and better treatment options. Age-related macular degeneration is divided into early-, intermediate- and late AMD. Late-stage AMD can take two forms: the fast-developing neovascular AMD (nAMD) and the more slowly progressing atrophic form, geographic atrophy (GA)

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