Persistent fetal ocular vasculature in mice deficient in bax and bak

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.