Visual Function and Survival of Injured Retinal Ganglion Cells in Aged Rbfox1 Knockout Animals.

Rbfox1 is a multifunctional RNA binding protein that regulates various aspects of RNA metabolism important for neuronal differentiation and normal physiology. Rbfox1 has been associated with neurodevelopmental and neurological conditions as well as age-related neurodegenerative diseases such as Alzheimer's and Parkinson's. We have shown that in mammalian retinas Rbfox1 is expressed in retinal ganglion cells (RGCs) and in amacrine cells (ACs).

Rbfox1 expression in amacrine cells is restricted to GABAergic and VGlut3 glycinergic cells.

Rbfox1 is a multifunctional RNA-binding protein that regulates alternative splicing, transcription, mRNA stability, and translation. Rbfox1 is an important regulator of gene networks involved in neurogenesis and neuronal function. Disruption of Rbfox function has been associated with several neurodevelopmental and neuropsychiatric disorders.

DNA and RNA oxidative damage in the retina is associated with ganglion cell mitochondria.

This study examines retinas from a rat glaucoma model for oxidized nucleosides 8OHdG and 8OHG, biomarkers for oxidative damage of DNA and RNA, respectively. Immunohistochemical data indicate a predominant localization of 8OHdG/8OHG in retinal ganglion cells (RGCs). The levels for these oxidized DNA/RNA products were 3.

Loss of Rbfox1 Does Not Affect Survival of Retinal Ganglion Cells Injured by Optic Nerve Crush.

Rbfox1 is a multifunctional RNA binding protein that regulates alternative splicing, transcription, mRNA stability and translation. Its roles in neurogenesis and neuronal functions are well established. Recent studies also implicate Rbfox1 in the regulation of gene networks that support cell survival during stress.

The effect of Rbfox2 modulation on retinal transcriptome and visual function.

Rbfox proteins regulate alternative splicing, mRNA stability and translation. These proteins are involved in neurogenesis and have been associated with various neurological conditions. Here, we analyzed Rbfox2 expression in adult and developing mouse retinas and the effect of its downregulation on visual function and retinal transcriptome.

Downregulation of splicing regulator RBFOX1 compromises visual depth perception.

Rbfox1 is a splicing regulator that has been associated with various neurological conditions such as autism spectrum disorder, mental retardation, epilepsy, attention-deficit/hyperactivity disorder and schizophrenia. We show that in adult rodent retinas, Rbfox1 is expressed in all types of retinal ganglion cells (RGCs) and in certain subsets of amacrine cells (ACs), within the inner nuclear (INL) and ganglion cell (GCL) layers. In the INL, all Rbfox1-positive cells were colocalized with GABAergic ACs, however not all GABAergic ACs were immunostained for Rbfox1.

RNA-binding protein Rbpms is represented in human retinas by isoforms A and C and its transcriptional regulation involves Sp1-binding site.

Rbpms (RNA-binding protein with multiple splicing) is a member of the RRM (RNA Recognition Motif) family of RNA-binding proteins, which is expressed as multiple alternatively spliced transcripts encoding different protein isoforms. We have shown earlier that Rbpms expression in the retina is restricted to retinal ganglion cells (RGCs), and have characterized this gene as a marker for RGCs. The aim of this study was to identify isoforms representing Rbpms in human retinas and to analyze its transcriptional regulation.

The effect of celastrol on the ocular hypertension-induced degeneration of retinal ganglion cells.

Celastrol, a quinine methide triterpene extracted from the perennial vine Tripterygium wilfordii, has been identified as a neuroprotective agent in various models of neurodegenerative disorders. We have reported earlier that systemic and intravitreal administration of celastrol stimulate the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC) and that mechanisms underlying celastrol׳s RGC protection may be associated with inhibition of TNF-alpha-mediated cell death. The present study evaluates the effect of celastrol on the survival of RGCs injured by ocular hypertension.

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival.

Heat shock proteins (HSPs) belong to a superfamily of stress proteins that are critical constituents of a complex defense mechanism that enhances cell survival under adverse environmental conditions. Cell protective roles of HSPs are related to their chaperone functions, antiapoptotic and antinecrotic effects. HSPs' anti-apoptotic and cytoprotective characteristics, their ability to protect cells from a variety of stressful stimuli, and the possibility of their pharmacological induction in cells under pathological stress make these proteins an attractive therapeutic target for various neurodegenerative diseases; these include Alzheimer's, Parkinson's, Huntington's, prion disease, and others.

Celastrol supports survival of retinal ganglion cells injured by optic nerve crush.

The present study evaluates the effect of celastrol on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). Celastrol, a quinine methide triterpene extracted from the perennial vine Tripterygium wilfordii (Celastraceae), has been identified as a potential neuroprotective candidate in a comprehensive drug screen against various neurodegenerative diseases. Two weeks after ONC, the average density of remaining RGCs in retinas of animals treated with daily intraperitoneal (i.

Crystallins in retinal ganglion cell survival and regeneration.

Crystallins are heterogeneous proteins classified into alpha, beta, and gamma families. Although crystallins were first identified as the major structural components of the ocular lens with a principal function to maintain lens transparency, further studies have demonstrated the expression of these proteins in a wide variety of tissues and cell types. Alpha crystallins (alpha A and alpha B) share significant homology with small heat shock proteins and have chaperone-like properties, including the ability to bind and prevent the precipitation of denatured proteins and to increase cellular resistance to stress-induced apoptosis.

The dark phase intraocular pressure elevation and retinal ganglion cell degeneration in a rat model of experimental glaucoma.

Intraocular pressure (IOP) elevation is considered as a major risk factor causing the progression of vision deterioration in glaucoma. Although it is known that the IOP level changes widely throughout the day and night, how the dark or light phase IOP elevation contributes to retinal ganglion cell (RGC) degeneration is still largely unclear. To examine the profile of IOP, modified laser photocoagulation was applied to the trabecular meshwork of Brown Norway rats and both light and dark phase IOPs were monitored approximately 1-2 times a week.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.

The neuronal EGF-related gene Nell2 interacts with Macf1 and supports survival of retinal ganglion cells after optic nerve injury.

Nell2 is a neuron-specific protein containing six epidermal growth factor-like domains. We have identified Nell2 as a retinal ganglion cell (RGC)-expressed gene by comparing mRNA profiles of control and RGC-deficient rat retinas. The aim of this study was to analyze Nell2 expression in wild-type and optic nerve axotomized retinas and evaluate its potential role in RGCs.

Quantitative analysis of retinal ganglion cell survival with Rbpms immunolabeling in animal models of optic neuropathies.

Purpose: To investigate whether a recently described retinal ganglion cell (RGC) marker Rbpms (RNA binding protein with multiple splicing) could be used for RGC quantification in various models of RGC degeneration.

Methods: Optic nerve crush, excitotoxicity, and elevated intraocular pressure (IOP) rat models were used. Topographic analysis of Rbpms immunolabeling was performed on retinal wholemounts.

Severe neurologic impairment in mice with targeted disruption of the electrogenic sodium bicarbonate cotransporter NBCe2 (Slc4a5 gene).

The choroid plexus lining the four ventricles in the brain is where the majority of cerebrospinal fluid (CSF) is produced. The secretory function of the choroid plexus is mediated by specific transport systems that allow the directional flux of nutrients and ions into the CSF and the removal of toxins. Normal CSF dynamics and chemistry ensure that the environment for neural function is optimal.

Asymmetric phenotype of Axenfeld-Rieger anomaly and aniridia associated with a novel PITX2 mutation.

Purpose: To evaluate the asymmetry of the anterior segment phenotype between the two eyes of a patient with Axenfeld-Rieger syndrome (ARS).

Methods: The entire database of a tertiary glaucoma practice was screened for patients with ARS. The medical records of patients with ARS were reviewed.

Thioredoxins 1 and 2 protect retinal ganglion cells from pharmacologically induced oxidative stress, optic nerve transection and ocular hypertension.

Oxidative damage has been implicated in retinal ganglion cell (RGC) death after optic nerve transection (ONT) and during glaucomatous neuropathy. Here, we analyzed the expression and cell protective role of thioredoxins (TRX), key regulators of the cellular redox state, in RGCs damaged by pharmacologically induced oxidative stress, ONT and elevated intraocular pressure (IOP). The endogenous level of thioredoxin-1 (TRX1) and thioredoxin-2 (TRX2) in RGCs after axotomy and in RGC-5 cells after glutamate/buthionine sulfoximine (BSO) treatment showed upregulation of TRX2, whereas no significant change was observed in TRX1 expression.

Overexpression of thioredoxins 1 and 2 increases retinal ganglion cell survival after pharmacologically induced oxidative stress, optic nerve transection, and in experimental glaucoma.

Purpose: Oxidative damage is implicated in retinal ganglion cell (RGC) death after optic nerve transection (ONT) and in glaucoma. We analyzed the expression and protective effects of thioredoxins (TRXs), regulators of the cellular reduction-oxidative (redox) state, in RGCs damaged by pharmacologically induced oxidative stress, ONT, and elevated intraocular pressure (IOP).

Methods: ONT and glaucoma models in the rat were used.

RNA binding protein with multiple splicing: a new marker for retinal ganglion cells.

Purpose: To characterize expression of the RNA binding protein (RBPMS) in the retina as a specific marker for retinal ganglion cells (RGCs).

Methods: Optic nerve transection (ONT) was performed on adult male Wistar rats. Retrograde RGC labeling was performed with FluoroGold (FG) applied to the cut surface of the optic nerve.

The role of alphaA- and alphaB-crystallins in the survival of retinal ganglion cells after optic nerve axotomy.

Purpose: Stress-induced crystallin expression is commonly viewed as activation of the cell survival mechanism. The authors analyzed the expression of alphaA- and alphaB-crystallins in a rat optic nerve transection (ONT) model characterized by specific retinal ganglion cell (RGC) degeneration and determined their role in RGC survival.

Methods: ONT was performed on adult Wistar rats.

Regulatory sequences in the 3' untranslated region of the human cGMP-phosphodiesterase beta-subunit gene.

Purpose: Rod cGMP-phosphodiesterase, a key enzyme in visual transduction, is important for retinal integrity and function. Mutations in the gene encoding the phosphodiesterase beta-subunit (PDEbeta) cause retinal degeneration in animals and humans. Here the authors tested the hypothesis that elements in the 3' untranslated region (3' UTR) of the PDEbeta gene are involved in the regulation of PDEbeta expression.

Non-invasive gene transfer by iontophoresis for therapy of an inherited retinal degeneration.

Despite extensive research on many of the genes responsible for inherited retinal degenerations leading to blindness, no effective treatment is currently available for patients affected with these diseases. Among the therapeutic approaches tested on animal models of human retinal degeneration, gene therapy using different types of viral vectors as delivery agents has yielded promising results. We report here our results on a non-invasive, non-viral delivery approach using transscleral iontophoresis for transfer of plasmid DNA into mouse retina.

Activation of autophagy in retinal ganglion cells.

Autophagy has been shown to be activated in neuronal cells in response to injury and suggested to have a cell-protective role in neurodegenerative diseases. In this study, we investigated the activation of autophagy in retinal ganglion cells (RGCs) following optic nerve transection (ONT) and evaluated its effect on RGC survival. Expression of several autophagy-related genes, including Atg5, Atg7, and Atg12, and autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1 were analyzed at the transcriptional or protein level 1, 3, and 7 days after ONT.

Protective effect of thioredoxins 1 and 2 in retinal ganglion cells after optic nerve transection and oxidative stress.

Purpose: Oxidative stress has been implicated in retinal ganglion cell (RGC) death pathways after optic nerve transection (ONT) and during glaucomatous neuropathy. The authors investigated the expression and cell-protective roles of thioredoxins (cytosolic Trx1 and mitochondrial Trx2), important regulators of the cellular redox state, on RGCs after ONT and pharmacologic oxidative stress induction.

Methods: ONT was performed on adult Wistar rats.