Neural stem/progenitor cells circulating in peripheral blood of patients with neovascular form of AMD: a novel view on pathophysiology

• Published in: Graefe's archive for clinical and experimental ophthalmology 2011-12, Vol.249 (12), p.1785-1794
• Main Authors: Machalińska, Anna, Kłos, Patrycja, Safranow, Krzysztof, Dziedziejko, Violetta, Rudnicki, Michał, Paczkowska, Edyta, Karczewicz, Danuta, Machaliński, Bogusław
• Format: Article
• Language: English
• Subjects: Age; Aged; Basic Science; Biomarkers - blood; Bone marrow; Chemokine CXCL12 - blood; Chemokines; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Fluorescent Antibody Technique, Indirect; Glial cells; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - genetics; Hemopoiesis; Humans; Intermediate Filament Proteins - genetics; Macular degeneration; Male; Medicine; Medicine & Public Health; Nerve Tissue Proteins - genetics; Nestin; Neural stem cells; Neural Stem Cells - physiology; Ophthalmology; Peripheral blood; Plasma levels; Real-Time Polymerase Chain Reaction; Receptors, CXCR4 - metabolism; Retinal Neurons - physiology; RNA, Messenger - blood; SDF-1 protein; Stem cells; Tubulin - genetics; vascularization; Wet Macular Degeneration - blood; Wet Macular Degeneration - physiopathology
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s00417-011-1767-9

Background The neovascular form of age-related macular degeneration (AMD) manifested with choroidal neovascularization (CNV) is one of the leading causes of rapid and irreversible visual loss. Recent reports suggest that bone marrow-derived stem/progenitor cells (SPCs) play a crucial role in the development and progression of the disease. The purpose of this study was to investigate whether or not undifferentiated non-haematopoietic stem cells, including those capable of differentiating into neural phenotypes, play a role in the pathological state of CNV formation. Methods Peripheral blood samples were collected from 46 patients diagnosed with CNV and from 46 controls. The CXCR4 + Lin - CD45 - stem cells were counted and analysed by flow cytometry. Using qRT-PCR and immunocytofluorescence, the expression of early neural and glial cell markers (β-III-tubulin, nestin, and glial fibrillary acidic protein) in the sorted cells was analysed, and correlated with plasma concentrations of stromal cell-derived factor 1 (SDF-1) (enzyme-linked immunosorbent assay), which is a pivotal chemokine that regulates the trafficking of SPCs. Results We found that the number of circulating CXCR4 + Lin - CD45 - cells did not differ in patients with active CNV as compared to the controls. However, we noticed significant intracellular overexpression of β-III-tubulin in the cells derived from AMD patients. Moreover, we observed significantly lower SDF-1 plasma levels in neovascular AMD patients compared to healthy individuals. Conclusions Our findings suggest that neural progenitor cells, together with low SDF-1 concentrations, may play a considerable role in the process of AMD progression. Further investigations aimed at the precise elucidation of these issues may help with the future development of effective prevention against, and the treatment of, this disease.