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.
Hahn
Paul
P
Departments of Medicine, Pathology, and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, USA.
Lindsten
Tullia
T
Tolentino
Michael
M
Thompson
Craig B
CB
Bennett
Jean
J
Dunaief
Joshua L
JL
D000818:Animals; D017209:Apoptosis; D005124:Eye Abnormalities / Q000209:etiology* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007908:Lens, Crystalline / Q000098:blood supply* / Q000473:pathology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009898:Optic Disk / Q000098:blood supply / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D014822:Vitreous Body / Q000002:abnormalities* / Q000473:pathology; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein