TY - JOUR
T1 - Pax6 heterozygous eyes show defects in chamber angle differentiation that are associated with a wide spectrum of other anterior eye segment abnormalities
AU - Baulmann, Daniela C.
AU - Ohlmann, Andreas
AU - Flügel-Koch, Cassandra
AU - Goswami, Sumanta
AU - Cvekl, Ales
AU - Tamm, Ernst R.
N1 - Funding Information:
Supported by grants from the American Health Assistance Foundation, Rockville, MD, USA and the Deutsche Forschungsgemeinschaft (SFB 539) (E.R.T.), and NIH grant EY12200 and Research to Prevent Blindness Career Development Award (A.C.). Pax6 lacZ/+ mice were generously provided by Peter Gruss, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany. The authors would like to thank Peter Gruss for helpful comments and discussion. In addition, the authors wish to thank Kathrin Baier, Anke Fischer, Karin Göhler and Antonia Kellenberger for their excellent technical assistance, and Marco Gößwein for his expert processing of the electron micrographs.
PY - 2002/10
Y1 - 2002/10
N2 - The development of the chamber angle was studied in the eyes of heterozygous Pax6lacZ/+ mutant mice (Nature 387 (1997) 406). Mutations in PAX6 cause aniridia, a condition that is frequently associated with glaucoma, a blinding disease that may be associated with chamber angle defects. Mesenchymal cells were seen in the chamber angle at P1-P5. In wild-type mice, these cells differentiated into typical trabecular meshwork (TM) cells next to Schlemm's canal. In Pax6lacZ/+ mice, TM cells remained undifferentiated and Schlemm's canal was absent. From P1 to P4, staining for β-galactosidase and immunoreactivity for Pax6 were observed in chamber angle mesenchyme, but were absent later. Cultured murine TM cells expressed Pax6. The defects in chamber angle and TM differentiation were associated with a wide spectrum of other anterior eye defects, which included various degrees of iris hypoplasia and corneal haze, isolated iridocorneal adhesions and atypical coloboma, and a vascularized cornea in all adult animals. A third of the animals showed Peters' anomaly including corneal opacity and iridocorneal adhesions. The separation of the lens from the cornea was incomplete, and epithelial layers of lens and cornea were continuous. Pax6 activity is directly required for differentiation of the chamber angle. Variations in phenotype of Pax6lacZ/+ mice appear not to involve direct dominant-negative or dose-dependent effects.
AB - The development of the chamber angle was studied in the eyes of heterozygous Pax6lacZ/+ mutant mice (Nature 387 (1997) 406). Mutations in PAX6 cause aniridia, a condition that is frequently associated with glaucoma, a blinding disease that may be associated with chamber angle defects. Mesenchymal cells were seen in the chamber angle at P1-P5. In wild-type mice, these cells differentiated into typical trabecular meshwork (TM) cells next to Schlemm's canal. In Pax6lacZ/+ mice, TM cells remained undifferentiated and Schlemm's canal was absent. From P1 to P4, staining for β-galactosidase and immunoreactivity for Pax6 were observed in chamber angle mesenchyme, but were absent later. Cultured murine TM cells expressed Pax6. The defects in chamber angle and TM differentiation were associated with a wide spectrum of other anterior eye defects, which included various degrees of iris hypoplasia and corneal haze, isolated iridocorneal adhesions and atypical coloboma, and a vascularized cornea in all adult animals. A third of the animals showed Peters' anomaly including corneal opacity and iridocorneal adhesions. The separation of the lens from the cornea was incomplete, and epithelial layers of lens and cornea were continuous. Pax6 activity is directly required for differentiation of the chamber angle. Variations in phenotype of Pax6lacZ/+ mice appear not to involve direct dominant-negative or dose-dependent effects.
KW - Cornea
KW - Iris
KW - Pax6
KW - Peters' anomaly
KW - Schlemm's canal
KW - Trabecular meshwork
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U2 - 10.1016/S0925-4773(02)00260-5
DO - 10.1016/S0925-4773(02)00260-5
M3 - Article
C2 - 12351165
AN - SCOPUS:0036805779
SN - 0925-4773
VL - 118
SP - 3
EP - 17
JO - Mechanisms of Development
JF - Mechanisms of Development
IS - 1-2
ER -