Human organotypic retinal cultures (HORCs) as a chronic experimental model for investigation of retinal ganglion cell degeneration

There is a growing need for models of human diseases that utilise native, donated human tissue in order to model disease processes and develop novel therapeutic strategies. In this paper we assessed the suitability of adult human retinal explants as a potential model of chronic retinal ganglion cell (RGC) degeneration. Our results confirmed that RGC markers commonly used in rodent studies (NeuN, bIII Tubulin and Thy-1) were appropriate for labelling human RGCs and followed the expected differential expression patterns across, as well as throughout, the macular and para-macular regions of the retina. Furthermore, we showed that neither donor age nor post-mortem time (within 24 h) significantly affected the initial expression levels of RGC markers. In addition, the feasibility of using human post mortem donor tissue as a long-term model of RGC degeneration was determined with RGC protein being detectable up to 4 weeks in culture with an associated decline in RGC mRNA and significant, progressive, apoptotic labelling of NeuNþ cells. Differences in RGC apoptosis might have been influenced by medium compositions indicating that media constituents could play a role in supporting axotomised RGCs. We propose that using ex vivo human explants may prove to be a useful model for testing the effectiveness of neuroprotective strategies

Egyptian Unbelievers\u27 Beliefs

Atheists have been overlooked by the Egyptian society for a long time. However, following the January 25th revolution in Egypt, atheists in the country are speaking up and calling for their rights to be integrated in the society. This documentary will allow few of Egyptian atheists to express their beliefs, and the difficulties they face. After the January 25th revolution, it is high time Egyptian atheists spoke up and called for their rights and to be integrated in the society. In this documentary Luciana Antonious talks to Egyptian atheists who express their beliefs and the difficulties they face in a Muslim majority country

Targeting the Phosphatidylinositide-3 Kinase Pathway and the Mitogen-activated-protein Kinase Pathway through Thymosin-beta4, Exercise, and Negative Regulators to Promote Retinal Ganglion Cell Survival or Regeneration

The phosphatidylinositide-3 kinase (PI3K) and mitogen-activated-protein kinase (MAPK) pathways mediate cellular survival in the presence of apoptotic stimuli. These pathways are known to promote the survival of injured retinal ganglion cells (RGCs), central nervous system neurons that project visual information from the retina to the brain. Injury to the optic nerve triggers apoptosis of RGCs. This work demonstrates that Thymosin-beta4, a peptide involved in actin sequestration, both enhances RGC survival after injury and increases axonal regeneration. Moreover, Thymosin-beta4 modulates the PI3K and MAPK pathways. In addition, this study demonstrates that exercise reduces apoptosis of injured RGCs, and explores the function of the PI3K and MAPK pathways in this process. Finally, small peptides are used to interfere with the functions of PTEN, a negative regulator of the PI3K pathway, as well as Erbin and BCR, negative regulators in the MAPK pathway. These peptides enhance RGC survival and axonal regeneration after injury.M.Sc.2017-06-14 00:00:0

A Rare Case of Bilateral Perioptic Neuritis from Giant Cell Arteritis

Giant cell arteritis (GCA) results in visual loss typically through anterior ischemic optic neuropathy (AION), posterior ischemic optic neuropathy, central retinal artery occlusion, or cilioretinal artery occlusion.1,2 Perioptic neuritis is very rare in GCA, and only few cases have been reported.3,4 We present a rare case of bilateral perioptic neuritis from GCA, with a component of AION that improved significantly with high-dose steroids

Neuronal injury external to the retina rapidly activates retinal glia, followed by elevation of markers for cell cycle re-entry and death in retinal ganglion cells

Retinal ganglion cells (RGCs) are neurons that relay visual signals from the retina to the brain. The RGC cell bodies reside in the retina and their fibers form the optic nerve. Full transection (axotomy) of the optic nerve is an extra-retinal injury model of RGC degeneration. Optic nerve transection permits time-kinetic studies of neurodegenerative mechanisms in neurons and resident glia of the retina, the early events of which are reported here. One day after injury, and before atrophy of RGC cell bodies was apparent, glia had increased levels of phospho-Akt, phospho-S6, and phospho-ERK1/2; however, these signals were not detected in injured RGCs. Three days after injury there were increased levels of phospho-Rb and cyclin A proteins detected in RGCs, whereas these signals were not detected in glia. DNA hyperploidy was also detected in RGCs, indicative of cell cycle re-entry by these post-mitotic neurons. These events culminated in RGC death, which is delayed by pharmacological inhibition of the MAPK/ERK pathway. Our data show that a remote injury to RGC axons rapidly conveys a signal that activates retinal glia, followed by RGC cell cycle re-entry, DNA hyperploidy, and neuronal death that is delayed by preventing glial MAPK/ERK activation. These results demonstrate that complex and variable neuro-glia interactions regulate healthy and injured states in the adult mammalian retina. © 2014 Galan et al.Peer Reviewe

Neuronal injury external to the retina rapidly activates retinal glia, followed by elevation of markers for cell cycle re-entry and death in retinal ganglion cells.

Retinal ganglion cells (RGCs) are neurons that relay visual signals from the retina to the brain. The RGC cell bodies reside in the retina and their fibers form the optic nerve. Full transection (axotomy) of the optic nerve is an extra-retinal injury model of RGC degeneration. Optic nerve transection permits time-kinetic studies of neurodegenerative mechanisms in neurons and resident glia of the retina, the early events of which are reported here. One day after injury, and before atrophy of RGC cell bodies was apparent, glia had increased levels of phospho-Akt, phospho-S6, and phospho-ERK1/2; however, these signals were not detected in injured RGCs. Three days after injury there were increased levels of phospho-Rb and cyclin A proteins detected in RGCs, whereas these signals were not detected in glia. DNA hyperploidy was also detected in RGCs, indicative of cell cycle re-entry by these post-mitotic neurons. These events culminated in RGC death, which is delayed by pharmacological inhibition of the MAPK/ERK pathway. Our data show that a remote injury to RGC axons rapidly conveys a signal that activates retinal glia, followed by RGC cell cycle re-entry, DNA hyperploidy, and neuronal death that is delayed by preventing glial MAPK/ERK activation. These results demonstrate that complex and variable neuro-glia interactions regulate healthy and injured states in the adult mammalian retina