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Is glutamate dehydrogenase in astrocytes one of the keys to control brain glutamate homeostasis?
SummaryBrain glutamate concentration needs to be balanced to avoid excitoxicity. Following glutamatergic neurotransmission astrocytes are responsible for clearance of the synaptic cleft via glutamate transporters. In the astrocyte the conversion of glutamate to glutamine is an essential part of the glutamate‐glutamine cycle. But, a substantial amount of glutamate is oxidatively metabolized in the mitochondria, which to a large extent may be dependent on glutamate dehydrogenase (GDH). Thus, astrocytes are likely the main regulator of the brain glutamate concentration, but how do they do it? We have investigated the role o...
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: H. Waagepetersen Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research

Regulating gene expression towards solving ocular surface diseases
SummaryTreatment of genetic eye disease poses significant medical and surgical challenges. We used a bioluminescent corneal reporter gene mouse model to assess efficacy and potency of a number of gene therapy approaches for corneal dystrophy. Various modalities were assessed for delivery of short interfering RNA (siRNA) targeting one of five mutant alleles present in the corneal bioluminescent mouse model enabling assessment of topical, subconjunctival and intrastromal delivery. Potent and sustained in vivo gene silencing >50% for up to 7 days was observed. This siRNA therapy only provides a transient silencing of the ...
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: T. Moore, S. Atkinson, E. Maurizi, D. Schiroli, L. Mairs, K. Christie, I. McLean, E. Allen, D.L. Pedrioli, J. Moore, A. Nesbit Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research

In vitro evaluation of anti HSV ‐1 siRNAs and in vivo evaluation of electroporation to transfect siRNAs on murine cornea
ConclusionsThese results demonstrate that siRNA directed against HSV‐1 DNA polymerase efficiently inhibits HSV‐1 replication, suggesting that siRNA based antiviral strategy may be a potential therapeutic alternative to treat HSK. Besides, intracorneal penetration may be facilitated by electroporation.
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: A. Rousseau, V. Escriou, P. Roy, N. Poccardi, J. Takissian, P. Bigey, M. Labetoulle Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research

Cytoprotective alpha crystallins in the regulation of RPE cell proteostasis
SummaryAlphaB‐Crystallin (αBC) is an ubiquitous protein with dual function as a molecular chaperone to preserve proteostasis and as an anti‐apoptotic agent. We studied the regulatory role of αBC in murine models of oxygen‐induced retinopathy (OIR), laser‐induced choroidal neovascularization (CNV) and subretinal fibrosis (SF). αBC KO attenuated retinal NV in OIR as compared to WT. In the laser model, CNV lesion size was significantly reduced in αBC KO vs. WT mice. VEGF increased 8 fold in WT vs. αBC KO on day 3 and 7 post‐laser and VEGF secretion was lower in αBC KO vs. WT. Increased mono (tetra)‐ubiquitin...
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: R. Kannan Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research