The regulatory roles of apoptosis-inducing factor in the formation and regression processes of ocular neovascularization

Toshio Hisatomi, shintaro nakao, yusuke murakami, Kousuke Noda, Toru Nakazawa, Shoji Notomi, Edward Connolly, Haicheng She, Lama Almulki, Yasuhiro Ito, Demetrios G. Vavvas, Tatsuro Ishibashi, Joan W. Miller

Research output: Contribution to journalArticle

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Abstract

The role of apoptosis in the formation and regression of neovascularization is largely hypothesized, although the detailed mechanism remains unclear. Inflammatory cells and endothelial cells both participate and interact during neovascularization. During the early stage, these cells may migrate into an angiogenic site and form a pro-angiogenic microenvironment. Some angiogenic vessels appear to regress, whereas some vessels mature and remain. The control mechanisms of these processes, however, remain unknown. Previously, we reported that the prevention of mitochondrial apoptosis contributed to cellular survival via the prevention of the release of proapoptotic factors, such as apoptosis-inducing factor (AIF) and cytochrome c. In this study, we investigated the regulatory role of cellular apoptosis in angiogenesis using two models of ocular neovascularization: laser injury choroidal neovascularization and VEGF-induced corneal neovascularization in AIF-deficient mice. Averting apoptosis in AIF-deficient mice decreased apoptosis of leukocytes and endothelial cells compared to wild-type mice and resulted in the persistence of these cells at angiogenic sites in vitro and in vivo. Consequently, AIF deficiency expanded neovascularization and diminished vessel regression in these two models. We also observed that peritoneal macrophages from AIF-deficient mice showed anti-apoptotic survival compared to wild-type mice under conditions of starvation. Our data suggest that AIF-related apoptosis plays an important role in neovascularization and that mitochondria-regulated apoptosis could offer a new target for the treatment of pathological angiogenesis.

Original languageEnglish
Pages (from-to)53-61
Number of pages9
JournalAmerican Journal of Pathology
Volume181
Issue number1
DOIs
Publication statusPublished - Jul 1 2012

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Apoptosis Inducing Factor
Apoptosis
Endothelial Cells
Pathologic Neovascularization
Corneal Neovascularization
Choroidal Neovascularization
Peritoneal Macrophages
Starvation
Cytochromes c
Vascular Endothelial Growth Factor A
Mitochondria
Lasers
Leukocytes
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

The regulatory roles of apoptosis-inducing factor in the formation and regression processes of ocular neovascularization. / Hisatomi, Toshio; nakao, shintaro; murakami, yusuke; Noda, Kousuke; Nakazawa, Toru; Notomi, Shoji; Connolly, Edward; She, Haicheng; Almulki, Lama; Ito, Yasuhiro; Vavvas, Demetrios G.; Ishibashi, Tatsuro; Miller, Joan W.

In: American Journal of Pathology, Vol. 181, No. 1, 01.07.2012, p. 53-61.

Research output: Contribution to journalArticle

Hisatomi, Toshio ; nakao, shintaro ; murakami, yusuke ; Noda, Kousuke ; Nakazawa, Toru ; Notomi, Shoji ; Connolly, Edward ; She, Haicheng ; Almulki, Lama ; Ito, Yasuhiro ; Vavvas, Demetrios G. ; Ishibashi, Tatsuro ; Miller, Joan W. / The regulatory roles of apoptosis-inducing factor in the formation and regression processes of ocular neovascularization. In: American Journal of Pathology. 2012 ; Vol. 181, No. 1. pp. 53-61.
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