Imbalances in mobilization and activation of pro-inflammatory and vascular reparative bone marrow-derived cells in diabetic retinopathy

Harshini Chakravarthy, Eleni Beli, Svetlana Navitskaya, Sandra O'Reilly, Qi Wang, Nermin Kady, Chao Huang, Maria B. Grant, Julia V. Busik

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Diabetic retinopathy is a sight-threatening complication of diabetes, affecting 65% of patients after 10 years of the disease. Diabetic metabolic insult leads to chronic low-grade inflammation, retinal endothelial cell loss and inadequate vascular repair. This is partly due to bone marrow (BM) pathology leading to increased activity of BM-derived pro-inflammatory monocytes and impaired function of BM-derived reparative circulating angiogenic cells (CACs). We propose that diabetes has a significant long-term effect on the nature and proportion of BM-derived cells that circulate in the blood, localize to the retina and home back to their BM niche. Using a streptozotocin mouse model of diabetic retinopathy with GFP BM-transplantation, we have demonstrated that BM-derived circulating pro-inflammatory monocytes are increased in diabetes while reparative CACs are trapped in the BM and spleen, with impaired release into circulation. Diabetes also alters activation of splenocytes and BM-derived dendritic cells in response to LPS stimulation. A majority of the BM-derived GFP cells that migrate to the retina express microglial markers, while others express endothelial, pericyte and Müller cell markers. Diabetes significantly increases infiltration of BMderived microglia in an activated state, while reducing infiltration of BM-derived endothelial progenitor cells in the retina. Further, control CACs injected into the vitreous are very efficient at migrating back to their BM niche, whereas diabetic CACs have lost this ability, indicating that the in vivo homing efficiency of diabetic CACs is dramatically decreased. Moreover, diabetes causes a significant reduction in expression of specific integrins regulating CAC migration. Collectively, these findings indicate that BM pathology in diabetes could play a role in both increased pro-inflammatory state and inadequate vascular repair contributing to diabetic retinopathy.

Original languageEnglish (US)
Article numbere0146829
JournalPLoS One
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2016

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diabetic retinopathy
Diabetic Retinopathy
blood vessels
Bone Marrow Cells
bone marrow
Blood Vessels
Bone
Bone Marrow
Chemical activation
Medical problems
diabetes
cells
retina
Retina
Endothelial cells
Pathology
monocytes
Monocytes
endothelial cells
Infiltration

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chakravarthy, H., Beli, E., Navitskaya, S., O'Reilly, S., Wang, Q., Kady, N., ... Busik, J. V. (2016). Imbalances in mobilization and activation of pro-inflammatory and vascular reparative bone marrow-derived cells in diabetic retinopathy. PLoS One, 11(1), [e0146829]. https://doi.org/10.1371/journal.pone.0146829

Imbalances in mobilization and activation of pro-inflammatory and vascular reparative bone marrow-derived cells in diabetic retinopathy. / Chakravarthy, Harshini; Beli, Eleni; Navitskaya, Svetlana; O'Reilly, Sandra; Wang, Qi; Kady, Nermin; Huang, Chao; Grant, Maria B.; Busik, Julia V.

In: PLoS One, Vol. 11, No. 1, e0146829, 01.01.2016.

Research output: Contribution to journalArticle

Chakravarthy, H, Beli, E, Navitskaya, S, O'Reilly, S, Wang, Q, Kady, N, Huang, C, Grant, MB & Busik, JV 2016, 'Imbalances in mobilization and activation of pro-inflammatory and vascular reparative bone marrow-derived cells in diabetic retinopathy', PLoS One, vol. 11, no. 1, e0146829. https://doi.org/10.1371/journal.pone.0146829
Chakravarthy, Harshini ; Beli, Eleni ; Navitskaya, Svetlana ; O'Reilly, Sandra ; Wang, Qi ; Kady, Nermin ; Huang, Chao ; Grant, Maria B. ; Busik, Julia V. / Imbalances in mobilization and activation of pro-inflammatory and vascular reparative bone marrow-derived cells in diabetic retinopathy. In: PLoS One. 2016 ; Vol. 11, No. 1.
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