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

Publication ,  Journal Article
Espinosa-Heidmann, DG; Malek, G; Mettu, PS; Caicedo, A; Saloupis, P; Gach, S; Dunnon, AK; Hu, P; Spiga, M-G; Cousins, SW
Published in: Invest Ophthalmol Vis Sci
November 13, 2013

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.

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Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

November 13, 2013

Volume

54

Issue

12

Start / End Page

7439 / 7449

Location

United States

Related Subject Headings

  • Ophthalmology & Optometry
  • Mice, Inbred C57BL
  • Mice
  • Macular Degeneration
  • Immunohistochemistry
  • Fundus Oculi
  • Follow-Up Studies
  • Fluorescein Angiography
  • Female
  • Disease Models, Animal
 

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Espinosa-Heidmann, D. G., Malek, G., Mettu, P. S., Caicedo, A., Saloupis, P., Gach, S., … Cousins, S. W. (2013). Bone marrow transplantation transfers age-related susceptibility to neovascular remodeling in murine laser-induced choroidal neovascularization. Invest Ophthalmol Vis Sci, 54(12), 7439–7449. https://doi.org/10.1167/iovs.13-12546
Espinosa-Heidmann, Diego G., Goldis Malek, Priyatham S. Mettu, Alejandro Caicedo, Peter Saloupis, Sarah Gach, Askia K. Dunnon, Peng Hu, Maria-Grazia Spiga, and Scott W. Cousins. “Bone marrow transplantation transfers age-related susceptibility to neovascular remodeling in murine laser-induced choroidal neovascularization.Invest Ophthalmol Vis Sci 54, no. 12 (November 13, 2013): 7439–49. https://doi.org/10.1167/iovs.13-12546.
Espinosa-Heidmann DG, Malek G, Mettu PS, Caicedo A, Saloupis P, Gach S, et al. Bone marrow transplantation transfers age-related susceptibility to neovascular remodeling in murine laser-induced choroidal neovascularization. Invest Ophthalmol Vis Sci. 2013 Nov 13;54(12):7439–49.
Espinosa-Heidmann, Diego G., et al. “Bone marrow transplantation transfers age-related susceptibility to neovascular remodeling in murine laser-induced choroidal neovascularization.Invest Ophthalmol Vis Sci, vol. 54, no. 12, Nov. 2013, pp. 7439–49. Pubmed, doi:10.1167/iovs.13-12546.
Espinosa-Heidmann DG, Malek G, Mettu PS, Caicedo A, Saloupis P, Gach S, Dunnon AK, Hu P, Spiga M-G, Cousins SW. Bone marrow transplantation transfers age-related susceptibility to neovascular remodeling in murine laser-induced choroidal neovascularization. Invest Ophthalmol Vis Sci. 2013 Nov 13;54(12):7439–7449.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

November 13, 2013

Volume

54

Issue

12

Start / End Page

7439 / 7449

Location

United States

Related Subject Headings

  • Ophthalmology & Optometry
  • Mice, Inbred C57BL
  • Mice
  • Macular Degeneration
  • Immunohistochemistry
  • Fundus Oculi
  • Follow-Up Studies
  • Fluorescein Angiography
  • Female
  • Disease Models, Animal