The role of crumbs genes in the vertebrate cornea.
OBJECTIVE
To evaluate the role of crumbs genes and related epithelial polarity loci in the vertebrate cornea.


METHODS
The authors used histologic analysis and electron microscopy to evaluate the corneas of zebrafish mutant for a crumbs locus oko meduzy (ome) and in mutants of four other loci, nagie oko (nok), heart and soul (has), mosaic eyes (moe), and ncad (formerly glass onion), that function in the same or related genetic pathways. In parallel, they performed an evaluation of corneas in human carriers of a crumbs gene, CRB1, and mutations using topography and biomicroscopy. The expression of the CRB1 gene in the normal human cornea was examined by polymerase chain reaction (PCR) and immunohistochemical staining.


RESULTS
The corneas of zebrafish mutants display severe abnormalities of the epithelial and stromal layers. The epithelial cells do not properly adhere to each other, and fluid-filled spaces form between them. In addition, the layering of the corneal stroma is poorly formed or absent. The corneas of human carriers of CRB1 mutations display shape deviations compared with what has been observed in normal individuals. A PCR product of the correct size was obtained from normal human corneal samples. Sequence analyses confirmed its identity to be the human CRB1 gene. Immunohistochemical staining using anti-CRB1 yielded positive brown deposits in the human cornea.


CONCLUSIONS
crumbs genes play a role in the differentiation of the vertebrate cornea. Corneal defects associated with crumbs gene mutations are very severe in the zebrafish model and, in comparison, appear clinically less pronounced in the human eye.
Beyer
Jill
J
Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Zhao
Xinping C
XC
Yee
Richard
R
Khaliq
Shagufta
S
McMahon
Timothy T
TT
Ying
Hongyu
H
Yue
Beatrice Y J T
BY
Malicki
Jarema J
JJ
D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D019573:Epithelium, Corneal / Q000002:abnormalities* / Q000473:pathology / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D014714:Vertebrates; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
C448939:CRB1 protein, human; C517151:Crb1 protein, zebrafish; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D029961:Zebrafish Proteins
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