Francisco Javier Carreras
University of Granada
Spain
Title: Immunohistochemistry of adheren junctions in the optic nerve head highlights potential fatal sites for aqueous humor-induced ionic stress and points to a new paradigm in glaucoma diagnosis and treatment
Biography
Biography: Francisco Javier Carreras
Abstract
Is aqueous humor toxicity the missing link in glaucoma? Glaucoma is a prevalent disease characterized by axonal loss related to difficulties in aqueous humor outflow that may manifest as increased intraocular pressure. We have shown in perfusion experiments that the optic nerve with a fluid-conducting paravascular glial sheat is easily permeable. There is increasing evidence that in some regions of the CNS, axons rely on lactate rather that glucose for their nourishment. We have communicated that based on the presence of transport molecules; lactate is the main energy source at the astrocyte-rich pre-laminar level of the optic nerve. Along with them, adherens junctions (AJ) rich in N-cadherin depend of calcium ion to maintain the binding. We study the response of the cultured pre-laminar tissue of the pig to calcium ion withdrawal by transmission electron (TEM) and confocal (CLSM) microscopes to detect changes in the exposed N-Cadherin attachments. There is an increase both in apoptosis and increase in the cleft separation in AJ in the cultured pre-laminar region with aqueous humor-levels of calcium reduction. Phosphorylation of Beta-Catenin shown by immune-labeling and incremented apoptosis as measured by Western Blot of caspases is both induced by calcium reduction. Altogether, this suggests that activation of the signaling system related to AJ triggers a wave of anoikis in astrocytes. Axon loss in glaucoma can be linked to astrocyte detachment provoked by aqueous misdirection through the optic nerve. This mechanism opens new avenues for pathogenetically-oriented treatment of axon loss and corresponding visual field defects in glaucoma.
