Growth factors/chemokines in diabetic vitreous and aqueous alter the function of bone marrow-derived progenitor (CD34+) cells in humans

Sankarathi Balaiya, Maria B. Grant, Joshua Priluck, Kakarla V. Chalam

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Ocular ischemic microenvironment plays a critical role in the progression of diabetic retinopathy (DR). In this study, we investigated the effect of vitreous and aqueous obtained from proliferative DR patients on the function of CD34+ cells derived from healthy humans. Human CD34+ cells were incubated with vitreous or aqueous of subjects with PDR. After incubation, cell migration of CD34+ was evaluated with CXCL12. Intracellular levels of nitric oxide (NO) were measured with DAF-FM. Tube formation assay was used to evaluate the effect of treated CD34+ cells on in vitro angiogenesis. Angiogenic protein array and mass spectrometry (MS) were performed to ascertain the factors secreted by healthy nondiabetic CD34+ cells exposed to diabetic vitreous or aqueous. PDR vitreous/aqueous reduced migration of CD34+ cells (672.45 ± 42.1/736.75 ± 101.7 AFU; P < 0.01) and attenuated intracellular NO levels (182 ± 1.4/184.5 ± 6.3 AFU, P = 0.002). Pretreatment with PDR vitreous suppressed tube formation of human retinal endothelial cells (64 ± 1.6 vs. 80 ± 2.5). CD34+ exposed to PDR vitreous resulted in the increased expression of CXCL4 and serpin F1, whereas CD34+ exposed to PDR aqueous showed increased expression of CXCL4, serpin F1, and endothelin-1 (ET-1). MS analysis of CD34+ (exposed to PDR vitreous) expressed J56 gene segment, isoform 2 of SPARC-related modular calcium-binding protein 2, isoform 1 of uncharacterized protein c1 orf167, integrin α-M, and 40s ribosomal protein s21. Exposure of healthy nondiabetic CD34+cells to PDR vitreous and aqueous resulted in decreased migration, reduced generation of NO, and altered paracrine secretory function. Our results suggest that the contribution of CD34+ cells to the aberrant neovascularization observed in PDR is driven more by the proangiogenic effects of the retinal cells rather than the influence of the vitreous.

Original languageEnglish (US)
Pages (from-to)E695-E702
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume307
Issue number8
DOIs
StatePublished - Oct 15 2014

Keywords

  • Aqueous
  • CD34
  • Progenitor cells
  • Proliferative diabetic retinopathy
  • Vitreous

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

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