Research Paper Volume 13, Issue 24 pp 25763—25777

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 Liisborg1,2, , Vibe Skov3, , Lasse Kjær3, , Hans Carl Hasselbalch2,3, , Torben Lykke Sørensen1,2, ,

  • 1 Department of Ophthalmology, Zealand University Hospital, Roskilde 4000, Denmark
  • 2 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
  • 3 Department of Hematology, Zealand University Hospital, Roskilde 4000, Denmark

Received: November 17, 2021       Accepted: December 13, 2021       Published: December 26, 2021
How to Cite

Copyright: © 2021 Liisborg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


AMD: age-related macular degeneration; BM: Bruch’s membrane; CALR: calreticulin gene; CI: 95% confidence interval; CM: central memory cells; CLI: chronic low-grade inflammation; EM: effector memory cells; EMRA: effector memory CD45Ra positive cells; ET: essential thrombocytosis; GA: geographic atrophy; iAMD: intermediate stage AMD; IQR: interquartile range; JAK2V617F: mutation in the JAK2 gene; MPL: MPL gene, the gene encoding the thrombopoietin receptor; MPN: myeloproliferative neoplasms; MPNd: patients with myeloproliferative neoplasms having drusen; MPNd: patients with myeloproliferative neoplasms having normal retinas; nAMD: neovascular AMD; NKR: natural killer cell receptor; PMF: primary myelofibrosis; PV: polycythemia vera; ROS: reactive oxygen species; RPE: retinal pigment epithelium; SASP: senescence-associated secretory phenotype.