Crb1 is a determinant of retinal apical Müller glia cell features.
Mutations in the human Crumbs homologue-1 (CRB1) gene cause retinal blinding diseases, such as Leber congenital amaurosis and retinitis pigmentosa. In the previous studies we have shown that Crb1 resides in retinal Müller glia cells and that loss of Crb1 results in retinal degeneration (particularly in the inferior temporal quadrant of the mouse eye). Degeneration is increased by exposure to white light. Here, we studied the role of light and aging to gain a better understanding of the factors involved in the progress of retinal disease. Our data reveal that light is neither sufficient nor required to induce retinal disorganization and degeneration in young Crb1(-/-) mutant mice, suggesting that it rather modulates the retinal phenotype. Gene expression profiling showed that expression of five genes is altered in light-exposed Crb1(-/-) mutant retinas. Three of the five genes are involved in chromosome stabilization (Pituitary tumor transforming gene 1 or Pttg1, Establishment of cohesion 1 homolog 1 or Esco1, and a gene similar to histone H2B). In aged retinas, degeneration of photoreceptors, inner retinal neurons, and retinal pigment epithelium was practically limited to the inferior temporal quadrant. Loss of Crb1 in Müller glia cells resulted in an irregular number and size of their apical villi. We propose that Crb1 is required to regulate number and size of these Müller glia cell villi. The subsequent loss of retinal integrity resulted in neovascularization, in which blood vessels of the choroid protruded into the neural retina.
van de Pavert
Serge A
SA
Department of Neuromedical Genetics, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences , Amsterdam, The Netherlands.
Sanz
Alicia Sanz
AS
Aartsen
Wendy M
WM
Vos
Rogier M
RM
Versteeg
Inge
I
Beck
Susanne C
SC
Klooster
Jan
J
Seeliger
Mathias W
MW
Wijnholds
Jan
J
D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D008027:Light / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008871:Microvilli / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010775:Photic Stimulation / Q000009:adverse effects; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
C453730:Crb1 protein, mouse; D009419:Nerve Tissue Proteins