BACKGROUND: The ocular fetal vasculature normally regresses by apoptosis but for unknown reasons fails to regress in the human disease persistent fetal vasculature. OBJECTIVE: To investigate whether proapoptotic Bcl-2 members, Bax and Bak, are involved in fetal vasculature regression. METHODS: Adult eyes from mice deficient in Bax and/or Bak were examined grossly and histologically for persistence of fetal vasculature. Vessels were identified by the presence of lumens and erythrocytes and by Factor VIII labeling. Eyes from postnatal day 7 mice were processed for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) analysis to determine if deficiency of Bax and Bak results in defective developmental apoptosis. RESULTS: Only bax(-/-)bak(-/-) eyes retained fetal vasculature into adulthood. This vasculature consisted of a hyaloid artery emerging from the optic nerve head and intravitreal and perilental vessels but not a pupillary membrane. At postnatal day 7, wild-type but not bax(-/-)bak(-/-) eyes had TUNEL-positive cells in the fetal vasculature. CONCLUSIONS: These data demonstrate that Bax and Bak serve overlapping functions in fetal vasculature regression, emphasizing the importance of apoptosis in developmental remodeling. Clinical Relevance Disruption of Bax and Bak results in persistent fetal vasculature in knockout mice, providing a model of the human disease persistent fetal vasculature to investigate its etiology and potential therapies.
BACKGROUND: The ocular fetal vasculature normally regresses by apoptosis but for unknown reasons fails to regress in the human disease persistent fetal vasculature. OBJECTIVE: To investigate whether proapoptotic Bcl-2 members, Bax and Bak, are involved in fetal vasculature regression. METHODS: Adult eyes from mice deficient in Bax and/or Bak were examined grossly and histologically for persistence of fetal vasculature. Vessels were identified by the presence of lumens and erythrocytes and by Factor VIII labeling. Eyes from postnatal day 7 mice were processed for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) analysis to determine if deficiency of Bax and Bak results in defective developmental apoptosis. RESULTS: Only bax(-/-)bak(-/-) eyes retained fetal vasculature into adulthood. This vasculature consisted of a hyaloid artery emerging from the optic nerve head and intravitreal and perilental vessels but not a pupillary membrane. At postnatal day 7, wild-type but not bax(-/-)bak(-/-) eyes had TUNEL-positive cells in the fetal vasculature. CONCLUSIONS: These data demonstrate that Bax and Bak serve overlapping functions in fetal vasculature regression, emphasizing the importance of apoptosis in developmental remodeling. Clinical Relevance Disruption of Bax and Bak results in persistent fetal vasculature in knockout mice, providing a model of the human disease persistent fetal vasculature to investigate its etiology and potential therapies.
Authors: Claudia M Garcia; Ying-Bo Shui; Meera Kamath; Justin DeVillar; Randall S Johnson; Hans-Peter Gerber; Napoleone Ferrara; Michael L Robinson; David C Beebe Journal: Exp Eye Res Date: 2008-08-20 Impact factor: 3.467