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T. Hasegawa, S. McLeod, I. Bhutto, T. Prow, C. Merges, S. Kim, G.A. Lutty; Immunohistochemical Analysis of Human Choroidal Vascular Development . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4196.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Little is known about normal choroidal vascular development in the fetal human eye. The purpose of this study is to define the temporal and spatial expression of growth factors and their receptors that could influence normal choroidal vascular development. Methods: Serial cryosections of fetal human choroids of 8–20 weeks gestation (WG) were examined immunohistochemically. Antibodies used were markers of endothelial cells (CD34, CD31), angioblasts and endothelial cells (CD39), proliferating cells (Ki67), growth factors (VEGF, Ang–2, SDF–1), and their receptors (Flk–1, Flt–1, Tie–2, CXCR4). Additionally, immunofluorescence with double labeling was used to identify which cells were proliferating. Results: At 8–9 WG, choriocapillaris was forming in all areas, but large choroidal vessels were just starting to form. At 20 WG, choriocapillaris was well formed, while large choroidal vessels had formed in the posterior areas but were still developing in the peripheral areas. Ki67 positive cells were associated with development of large choroidal vessels. Some Ki67 positive cells were also positive for CD34 and/or CD39. Flk–1 was expressed in choriocapillaris and choroidal large vessels throughout development, while Flt–1 gradually increased. VEGF was weakly positive. Tie–2 was expressed in endothelial cells of choriocapillaris and large choroidal vessels at all times studied, but Ang–2 was predominantly localized ablumenally around large choroidal vessels. SDF–1 had the strongest immunoreactivity around choriocapillaris at 16 WG, while CXCR4 was associated with a few choroidal vessels.Conclusions:Choroidal vessels were developing through the period we examined (8–20WG). Choriocapillaris formed first, and then large choroidal vessels seemed to bud from them. The development of large choroidal vessels seemed to occur by angiogenesis since proliferation was apparent. Flk–1 and Tie–2 were associated with the choroidal vascular development as early as 8WG, while Flt–1, Ang–2 and SDF–1 were associated with later choroidal vascular development.
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