Patrolling monocytes are recruited and activated by diabetes to protect retinal microvessels

Francesco Tecilazich, Toan A. Phan, Fabio Simeoni, Giulia Maria Scotti, Zeina Dagher, Mara Lorenzi

Research output: Contribution to journalArticlepeer-review

Abstract

In diabetes there is a long latency between the onset of hyperglycemia and the appearance of structural micro-angiopathy. Because Ly6Clow patrolling monocytes (PMo) behave as housekeepers of the vasculature, we tested whether PMo protect microvessels against diabetes. We found that in wild-type mice, diabetes reduced PMo in the general circulation but increased by fourfold the absolute number of PMo adherent to retinal vessels (leukostasis). Conversely, in diabetic NR4A1-/- mice, a model of absence of PMo, there was no increase in leukostasis, and at 6 months of diabetes, the number of retinal acellular capillaries almost doubled compared with diabetic wild-type mice. Circulating PMo showed gene expression changes indicative of enhanced migratory, vasculopro-tective, and housekeeping activities, as well as profound suppression of genes related to inflammation and apo-ptosis. Promigratory CXCR4 was no longer upregulated at longer duration when retinal acellular capillaries begin to increase. Thus, after a short diabetes duration, PMo are the cells preferentially recruited to the retinal vessels and protect vessels from diabetic damage. These observations support the need for reinterpretation of the functional meaning of leukostasis in diabetes and document within the natural history of diabetic retinopathy pro-cesses of protection and repair that can provide novel paradigms for prevention.

Original languageEnglish
Pages (from-to)2709-2719
Number of pages11
JournalDiabetes
Volume69
Issue number12
DOIs
Publication statusPublished - Dec 2020

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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