Fiche du document
2013
- doi: 10.1371/journal.pone.0081600
- issn: 1932-6203
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0081600
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/24312324
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1932-6203
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_22380EAFA41A3
info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer
Sujets proches
Retinal Vitamin A aldehyde Retinaldehyde RetineneCiter ce document
S. Omri et al., « PKCζ Mediates Breakdown of Outer Blood-Retinal Barriers in Diabetic Retinopathy. », Serveur académique Lausannois, ID : 10.1371/journal.pone.0081600
Métriques
Partage / Export
Résumé
AIMS/HYPOTHESIS: Diabetic macular edema represents the main cause of visual loss in diabetic retinopathy. Besides inner blood retinal barrier breakdown, the role of the outer blood retinal barrier breakdown has been poorly analyzed. We characterized the structural and molecular alterations of the outer blood retinal barrier during the time course of diabetes, focusing on PKCζ, a critical protein for tight junction assembly, known to be overactivated by hyperglycemia. METHODS: Studies were conducted on a type2 diabetes Goto-Kakizaki rat model. PKCζ level and subcellular localization were assessed by immunoblotting and immunohistochemistry. Cell death was detected by TUNEL assays. PKCζ level on specific layers was assessed by laser microdissection followed by Western blotting. The functional role of PKCζ was then evaluated in vivo, using intraocular administration of its specific inhibitor. RESULTS: PKCζ was localized in tight junction protein complexes of the retinal pigment epithelium and in photoreceptors inner segments. Strikingly, in outer segment PKCζ staining was restricted to cone photoreceptors. Short-term hyperglycemia induced activation and delocalization of PKCζ from both retinal pigment epithelium junctions and cone outer segment. Outer blood retinal barrier disruption and photoreceptor cone degeneration characterized long-term hyperglycemia. In vivo, reduction of PKCζ overactivation using a specific inhibitor, restored its tight-junction localization and not only improved the outer blood retinal barrier, but also reduced photoreceptor cell-death. CONCLUSIONS: In the retina, hyperglycemia induced overactivation of PKCζ is associated with outer blood retinal barrier breakdown and photoreceptor degeneration. In vivo, short-term inhibition of PKCζ restores the outer barrier structure and reduces photoreceptor cell death, identifying PKCζ as a potential target for early and underestimated diabetes-induced retinal pathology.