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Choroidal Neovascularization Is Provided by Bone Marrow Cells

^a First Department of Pathology;
^b Department of Ophthalmology;
^c Regeneration Research Center for Intractable Disease;
^d Department of Anatomical Pathology;
^e Transplantation Center, Kansai Medical University, Moriguchi City, Osaka, Japan

Key Words. Choroidal neovascularization • Bone marrow cells • Age-related macular degeneration • Bone marrow transplantation

Susumu Ikehara, M.D., First Department of Pathology, Kansai Medical University, Fumizono-cho, Moriguchi City, Osaka, Japan, 570-8506. Telephone: 81-6-6992-1001 (ext. 2474 or 2475); Fax: 81-6-6992-1219; e-mail: ikehara{at}takii.kmu.ac.jp

Choroidal neovascularization (CNV) is a known cause of age-related macular degeneration (ARMD). Moreover, the most common cause of blindness in the elderly in advanced countries is ARMD with CNV. It has recently been shown that bone marrow cells (BMCs) can differentiate into various cell lineages in vitro and in vivo. Adults maintain a reservoir of hematopoietic stem cells included in BMCs that can enter the circulation to reach various organs in need of regeneration. It has recently been reported that endothelial progenitor cells (EPCs) included in BMCs are associated with neovascularization. We examine the role of BMCs in CNV using a model of CNV in adult mice. Using methods consisting of fractionated irradiation (6.0 Gy x 2) followed by bone marrow transplantation (BMT), adult mice were engrafted with whole BMCs isolated from transgenic mice expressing enhanced green fluorescent protein (EGFP). Three months after BMT, we confirmed that the hematopoietic cells in the recipients had been completely replaced with donor cells. We then carried out laser photocoagulation to induce CNV in chimeric mice (donor cells >95%). Two weeks after the laser photocoagulation, by which time CNV had occurred, immunohistochemical examination was carried out. The vascular wall cells of the CNV expressed both EGFP and CD31. These findings indicate that newly developed blood vessels in the CNV are derived from the BMCs and suggest that the inhibition of EPC mobilization from the bone marrow to the eyes could be a new approach to the fundamental treatment of CNV in ARMD.

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