Proteasomal Dysfunction results in ER stress, Endo MT, oxidative stress, and apoptotic cell death resulting in Fuchs Corneal Endothelial Dystrophy like features in mice
Murugan, S.; Ghag, S. A.; Souza de Campos, V.; Pan, H.-Y.; Price, M. O.; Price, F. W.; Shyam, R.
Show abstract
Fuchs Endothelial Corneal Dystrophy (FECD) is the irreversible degeneration of the corneal endothelium. The only treatment is corneal transplantation. To develop therapies for FECD, identifying the cellular causes for the onset and progression of the disease is crucial. While cell culture studies associate elevated oxidative stress, endoplasmic reticulum stress, endothelial-to-mesenchymal transition, and apoptosis with FECD, the causes behind the disease onset remain elusive. Guttae or Descemets membrane deposits are the earliest phenotype associated with FECD and are composed of unfolded proteins. Therefore, we asked if aberrant protein clearance pathways could be responsible for disease pathogenesis. We discovered a dysfunctional ubiquitin-proteasome pathway in a FECD mouse model and end-stage FECD patient samples. Inhibiting the ubiquitin-proteasome pathway in primary corneal endothelial cells resulted in the cellular dysfunctions associated with FECD. Finally, injecting healthy wild-type mice with proteasomal inhibitors resulted in all the major phenotypes associated with FECD, including corneal edema, guttae, and corneal endothelial cell loss. Therefore, this study strongly connects proteasomal dysfunction in FECD onset and progression.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Neuroretinal-derived caveolin-1 promotes endotoxin-induced inflammation in the murine retina 95%
- Spatially-Resolved Proteomic Analysis of the Lens Extracellular Diffusion Barrier 94%
- Intermittent hypoxia promotes functional neuroprotection from retinal ischemia in untreated first-generation offspring 94%
Similar papers in this journal
- A Cell Penetrating Peptide from Type I Interferon Protects the Retina in a Mouse Model of Autoimmune Uveitis 96%
- Ccr2 suppression by minocycline in Cx3cr1/Ccr2-visualized inherited retinal degeneration 95%
- Calcium dobesilate reduces VEGF signaling by interfering with heparan sulfate binding site and protects from vascular complications in diabetic mice 93%
Similar papers in this journal
- Lysophosphatidylcholine acyltransferase 1 controls the mitochondrial reactive oxygen species generation and survival of the retinal photoreceptor cells 95%
- CD44 inhibits α-SMA gene expression via a novel G-actin/MRTF mediated pathway that requires TGFβR/p38MAPK activity in murine skin fibroblasts. 92%
- Droplets of amyotrophic lateral sclerosis-associated p62/SQSTM1 mutants show slower inner fluidity 92%
Similar papers in this journal
- C1q limits cystoid edema by maintaining basal beta-catenin-dependent signaling and blood-retina barrier function 95%
- GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology 94%
- ERK hyperactivation in epidermal keratinocytes impairs intercellular adhesion and drives Grover disease pathology 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.