Glaucoma is the second leading cause of blindness in the United States, first among African Americans. In many cases, malformation of the eye, especially the iris and associated tissues, is the underlying cause of glaucoma. At present, little is known about basic mechanisms which contribute to normal iris development and therefore the pathology arising during abnormal development is not understood. The PI's laboratory has identified a new transcription factor, 1mx-1a, which is essential for normal iris development in mice. Mice which lack 1mx-1a have small eyes and a malformed iris. In the proposed research, the PI plans to extend our current findings in five distinct areas: First, the precise nature and timing of ocular developmental defects in our 1mx-1a mutant mice will be determined. Second, the functional relationship between 1mx-1a and other regulatory genes known to aniridia (total or partial loss of iris) and glaucoma in humans will be examined. Third, novel inductive mechanisms underlying anterior segment morphogenesis will be characterized using reagents we have generated and/or isolated. Fourth, the ability of cells lacking 1mx-1a to participate in normal eye development will be determined by the generation of chimeric mice. Finally, the human 1mx-1a gene will be isolated and mapped to determine if it may contribute to any hereditary glaucomas. Taken together, the proposed studies should lead to some of the first insights into important and essential molecular genetic mechanisms of anterior segment development. Progress in these areas will ultimately lead to fundamental advances in early diagnosis, treatment, and where possible prevention of pediatric and other hereditary glaucomas.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012311-03
Application #
6179050
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Liberman, Ellen S
Project Start
1998-07-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$278,015
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Biochemistry
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Liu, Pu; Johnson, Randy L (2010) Lmx1b is required for murine trabecular meshwork formation and for maintenance of corneal transparency. Dev Dyn 239:2161-71
Gould, Douglas B; Reedy, Mark; Wilson, Lawriston A et al. (2006) Mutant myocilin nonsecretion in vivo is not sufficient to cause glaucoma. Mol Cell Biol 26:8427-36
Chen, You-Tzung; Kobayashi, Akio; Kwan, Kin Ming et al. (2006) Gene expression profiles in developing nephrons using Lim1 metanephric mesenchyme-specific conditional mutant mice. BMC Nephrol 7:1
Dunston, Jennifer A; Reimschisel, Tyler; Ding, Yu-Qiang et al. (2005) A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression. Eur J Hum Genet 13:330-5
Kos, R; Reedy, M V; Johnson, R L et al. (2001) The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos. Development 128:1467-79