Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination.
Mutations in CRB1, the human homolog of Drosophila Crumbs, cause autosomal recessive blinding disorders of the retina. Whereas Crumbs is implicated in apical-basal epithelial polarity and photoreceptor morphogenesis, the role of CRB1 in normal or diseased retina remains unclear. We characterized the retinal organization in vivo of patients with CRB1 mutations and found that, unlike other inherited retinal degenerations studied to date, the CRB1 mutant retinas are remarkably thick in cross-section and lack the distinct layers of normal adult retina. There are coarse outer and inner zones and a thick surface layer around the optic nerve. The abnormal retinal architecture in CRB1 mutations resembles that of immature normal retina. The results suggest that the CRB1 disease pathway disturbs the development of normal human retinal organization by interrupting naturally occurring apoptosis.
Jacobson
Samuel G
SG
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. jacobsos@mail.med.upenn.edu
Cideciyan
Artur V
AV
Aleman
Tomas S
TS
Pianta
Michael J
MJ
Sumaroka
Alexander
A
Schwartz
Sharon B
SB
Smilko
Elaine E
EE
Milam
Ann H
AH
Sheffield
Val C
VC
Stone
Edwin M
EM
D005136:Eye Proteins; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009900:Optic Nerve / Q000002:abnormalities; D012160:Retina / Q000002:abnormalities* / Q000196:embryology
C448939:CRB1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins