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| Status |
Public on Jan 01, 2024 |
| Title |
Uveitic glaucoma-like features in Yap conditional knockout mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Glaucoma is a multifactorial neurodegenerative disease characterized by the progressive and irreversible degeneration of the optic nerve and retinal ganglion cells. Despite medical advances aiming at slowing degeneration down, around 40% of treated glaucomatous patients will undergo vision loss. It is thus of utmost importance to have a better understanding of the disease and to investigate more deeply its early causes. The transcriptional coactivator YAP, an important regulator of eye homeostasis, has recently drawn attention in the glaucoma research field. Here we show that Yap conditional knockout mice (Yap cKO), in which the deletion of Yap is induced in both Müller glia (i.e. the only retinal YAP-expressing cells) and the non-pigmented epithelial cells of the ciliary body, exhibit a breakdown of the aqueous-blood barrier, accompanied by a progressive collapse of the ciliary body. A similar phenotype is observed in human samples that we obtained from patients presenting with uveitis. In addition, aged Yap cKO mice harbor glaucoma-like features, including deregulation of key homeostatic Müller-derived proteins, retinal vascular defects, optic nerve degeneration and retinal ganglion cell death. Finally, transcriptomic analysis of Yap cKO retinas pointed to early-deregulated genes involved in extracellular matrix organization potentially underlying the onset and/or progression of the observed phenotype. Together, our findings reveal the essential role of YAP in preserving the integrity of the ciliary body and retinal ganglion cells, thereby preventing the onset of uveitic glaucoma-like features.
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| Overall design |
Comparative gene expression analysis of three mouse retinas dissected either from Yapfl/fl wild-type eyes or from Yapfl/fl;RaxCreERT2 to unravel the molecular signature that could explain the uveitic glauoma-like phenotype of Yap cKO mice.
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| Contributor(s) |
Bitard J, Grellier E, Lourdel S, Prior-Filipe H, Hamon A, Fenaille F, Castelli FA, Chu-Van E, Roger JE, Locker M, Perron M |
| Citation(s) |
38272861 |
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| Submission date |
Dec 20, 2023 |
| Last update date |
Feb 09, 2024 |
| Contact name |
Jerome Eric Roger |
| E-mail(s) |
jeromeeroger@gmail.com
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| Phone |
+33169156835
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| Organization name |
CNRS-Universite Paris Sud
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| Department |
CERTO
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| Lab |
Neuro-PSI
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| Street address |
151 Route de la Rotonde, Campus CEA Saclay - Bat 151
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| City |
Saclay |
| State/province |
Please select |
| ZIP/Postal code |
91400 |
| Country |
France |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1055063 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE251685_YAP-CKO-2M-Counts.txt.gz |
3.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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