Eyelid closure in embryogenesis is required for ocular adnexa development.
OBJECTIVE
Mammalian eye development requires temporary fusion of the upper and lower eyelids in embryogenesis. Failure of lid closure in mice leads to an eye open at birth (EOB) phenotype. Many genetic mutant strains develop this phenotype and studies of the mutants lead to a better understanding of the signaling mechanisms of morphogenesis. The present study investigates the roles of lid closure in eye development.


METHODS
Seven mutant mouse strains were generated by different gene ablation strategies that inactivated distinct signaling pathways. These mice, including systemic ablation of Map3k1 and Dkk2, ocular surface epithelium (OSE) knockout of c-Jun and Egfr, conditional knockout of Shp2 in stratified epithelium (SE), as well as the Map3k1/Jnk1 and Map3k1/Rhoa compound mutants, all exhibited defective eyelid closure. The embryonic and postnatal eyes in these mice were characterized by histology and immunohistochemistry.


RESULTS
Some eye abnormalities, such as smaller lens in the Map3k1-null mice and Harderian gland hypoplasia in the Dkk2-null mice, appeared to be mutant strain-specific, whereas other abnormalities were seen in all mutants examined. The common defects included corneal erosion/ulceration, meibomian gland hypoplasia, truncation of the eyelid tarsal muscles, failure of levator palpebrae superioris (LPS) extension into the upper eyelid and misplacement of the inferior oblique (IO) muscle and inferior rectus (IR) muscle. The muscle defects were traced to the prenatal fetuses.


CONCLUSIONS
In addition to providing a protective barrier for the ocular surface, eyelid closure in embryogenesis is required for the development of ocular adnexa, including eyelid and extraocular muscles.
Department of Environmental Health, University of Cincinnati, College of Medicine, Cincinnati, Ohio, United States.
Qinghang
Q
Meng
Department of Environmental Health, University of Cincinnati, College of Medicine, Cincinnati, Ohio, United States.
Maureen
M
Mongan
Department of Environmental Health, University of Cincinnati, College of Medicine, Cincinnati, Ohio, United States.
Vinicius
V
Carreira
Department of Environmental Health, University of Cincinnati, College of Medicine, Cincinnati, Ohio, United States.
Hisaka
H
Kurita
Ophthalmology, University of Cincinnati, College of Medicine, Cincinnati, Ohio, United States.
Chia-Yang
CY
Liu
Ophthalmology, University of Cincinnati, College of Medicine, Cincinnati, Ohio, United States.
Winston W-Y
WW
Kao
Department of Environmental Health, University of Cincinnati, College of Medicine, Cincinnati, Ohio, United States Ophthalmology, University of Cincinnati, College of Medicine, Cincinnati, Ohio, United States.
Ying
Y
Xia
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics*; D005143:Eyelids / Q000196:embryology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015151:Immunoblotting; D007150:Immunohistochemistry; D008537:Meibomian Glands / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011247:Pregnancy; D011270:Pregnancy, Animal; D015398:Signal Transduction
D005136:Eye Proteins; D004247:DNA
LPS; embryonic eyelid closure; extraocular muscles; ocular adnexa; tarsal muscles