Perinatal ablation of the mouse lens causes multiple anterior chamber defects.
OBJECTIVE
The purpose of this study was to reassess the role of the lens as an "embryonic organizer" of ocular tissues.


METHODS
We ablated the lens in mice by lens-specific expression of an attenuated version of diphtheria toxin A subunit(Tox176) driven by a modified crystallin promoter. Alterations in the differentiation programs of ocular tissues were examined by hematoxylin and eosin staining, in situ hybridization, and immunohistochemistry.


RESULTS
Transgenic mice in the family OVE1757 exhibited severe microphakia. Apoptotic lens fibers were seen by embryonic day 15 (E15) and the lenses were completely ablated by post natal day 8. Multiple defects were seen in the anterior chamber. Corneal endothelial cells did not differentiate properly. The mesenchymal cells that would normally give rise to the endothelial layer were found to express N-cadherin, but they failed to form tight junctions and undergo a mesenchymal-to-epithelial transition. Although early specification of the presumptive ciliary body and iris was detected, subsequent differentiation of the iris was blocked. No dramatic changes were seen in the development of the retina.


CONCLUSIONS
These results support the hypothesis that an intact lens is essential for proper differentiation of both the corneal endothelium and the iris and that the lens "organizes" the development of tissues in the anterior chamber.
Zhang
Yan
Y
Department of Surgery, Creighton University, Omaha, NE 68178, USA.
Overbeek
Paul A
PA
Govindarajan
Venkatesh
V
D000818:Animals; D000831:Animals, Newborn / Q000002:abnormalities / Q000235:genetics; D000867:Anterior Chamber / Q000002:abnormalities*; D001035:Aphakia / Q000150:complications* / Q000151:congenital*; D002454:Cell Differentiation; D004167:Diphtheria Toxin; D004728:Endothelium, Corneal / Q000002:abnormalities; D005260:Female; D005325:Fetal Organ Maturity / Q000235:genetics; D007498:Iris / Q000002:abnormalities; D007908:Lens, Crystalline / Q000002:abnormalities*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008850:Microphthalmos / Q000209:etiology; D038081:Organogenesis / Q000235:genetics; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012160:Retina / Q000196:embryology
D004167:Diphtheria Toxin