Bone marrow transplantation transfers age-related susceptibility to neovascular remodeling in murine laser- induced choroidal neovascularization

Diego G. Espinosa-Heidmann, Goldis Malek, Priyatham S. Mettu, Alejandro Caicedo, Peter Saloupis, Sarah Gach, Askia K. Dunnon, Peng Hu, Maria Grazia Spiga, Scott W. Cousins

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Purpose. Neovascular remodeling (NVR), the progression of small capillaries into large-caliber arterioles with perivascular fibrosis, represents a major therapeutic challenge in neovascular age-related macular degeneration (AMD). Neovascular remodeling occurs after laser-induced choroidal neovascularization (CNV) in aged but not young mice. Additionally, bone marrow-derived cells, including macrophages, endothelial precursor cells, and mesenchymal precursor cells, contribute to CNV severity. In this study, we investigated the impact of aged bone marrow transplantation (BMT) on the degree of fibrosis, size, and vascular morphology of CNV lesions in a mouse model of laser-induced CNV. Methods. Young (2 months) and old (16 months) mice were transplanted with green fluorescent protein (GFP)-labeled bone marrow isolated from either young or old donors. Laser CNV was induced 1 month following transplant, and eyes were analyzed via choroidal flat mounts and immunohistochemistry 1 month postlaser. The identity of cells infiltrating CNV lesions was determined using specific markers for the labeled transplanted cells (GFP+), macrophages (F4/80+), perivascular mesenchymal-derived cells (smooth muscle actin, SMA+), and endothelial cells (CD31+). Results. Bone marrow transplantation from aged mice transferred susceptibility to NVR into young recipients. Inversely, transplantation of young marrow into old mice prevented NVR, preserving small size and minimal fibrosis. Mice with NVR demonstrated a greater relative contribution of marrow-derived SMA+ perivascular mesenchymal cells as compared to other cells. Conclusions. Our findings indicate that the status of bone marrow is an important determining factor of neovascular severity. Furthermore, we find that perivascular mesenchymal cells, rather than endothelial cells, derived from aged bone marrow may contribute to increased CNV severity in this murine model of experimental neovascularization.

Original languageEnglish (US)
Pages (from-to)7439-7449
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number12
DOIs
StatePublished - Oct 17 2013
Externally publishedYes

Keywords

  • Age-related macular degeneration
  • Bone marrow transplantation
  • Bone marrow-derived perivascular precursor cells
  • Experimental choroidal neovascularization
  • Neovascular remodeling

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Bone marrow transplantation transfers age-related susceptibility to neovascular remodeling in murine laser- induced choroidal neovascularization'. Together they form a unique fingerprint.

  • Cite this