Abstract:
:The eye has become an excellent target for gene therapy, and gene augmentation therapy of inherited retinal disorders has made major progress in recent years. Nevertheless, a recent study indicated that gene augmentation intervention might not stop the progression of retinal degeneration in patients. In addition, for many genes, viral-mediated gene augmentation is currently not feasible due to gene size and limited packaging capacity of viral vectors as well as expression of various heterogeneous isoforms of the target gene. Thus, alternative gene-based strategies to stop or delay the retinal degeneration are necessary. This review focuses on an alternative pharmacologic treatment strategy based on the usage of translational read-through inducing drugs (TRIDs) such as PTC124, aminoglycoside antibiotics, and designer aminoglycosides for overreading in-frame nonsense mutations. This strategy has emerged as an option for up to 30-50% of all cases of recessive hereditary retinal dystrophies. In-frame nonsense mutations are single-nucleotide alterations within the gene coding sequence resulting in a premature stop codon. Consequently, translation of such mutated genes leads to the synthesis of truncated proteins, which are unable to fulfill their physiologic functions. In this context, application of TRIDs facilitates the recoding of the premature termination codon into a sense codon, thus restoring syntheses of full-length proteins. So far, clinical trials for non-ocular diseases have been initiated for diverse TRIDs. Although the clinical outcome is not analyzed in detail, an excellent safety profile, namely for PTC124, was clearly demonstrated. Moreover, recent data demonstrated sustained read-through efficacies of nonsense mutations causing retinal degeneration, as manifested in the human Usher syndrome. In addition, a strong retinal biocompatibility for PTC124 and designer aminoglycosides has been demonstrated. In conclusion, recent progress emphasizes the potential of TRIDs as an alternative pharmacologic treatment strategy for treating nonsense mutation-based retinal disorders.
journal_name
Vis Neuroscijournal_title
Visual neuroscienceauthors
Nagel-Wolfrum K,Möller F,Penner I,Wolfrum Udoi
10.1017/S0952523814000194subject
Has Abstractpub_date
2014-09-01 00:00:00pages
309-16issue
4-5eissn
0952-5238issn
1469-8714pii
S0952523814000194journal_volume
31pub_type
杂志文章,评审abstract::Observers performed red-green and yellow-blue hue cancellation tasks for a 0.8-deg circular test field on a dark surround, by manipulating the excitation level of one cone class while the other two classes were held constant. The results of the red-green judgments conformed to classical opponent color theory in that b...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523801186062
更新日期:2001-11-01 00:00:00
abstract::We examine the assumptions that the fovea contains equal numbers of inner (invaginating or ON) and outer (flat or OFF) midget bipolar cells and equal numbers of inner and outer diffuse bipolar cells. Based on reconstruction from electron photomicrographs of serial thin sections through the fovea of a macaque monkey, w...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523803202091
更新日期:2003-03-01 00:00:00
abstract::A series of psychophysical tests examining early and later aspects of image-motion processing were conducted in a patient with bilateral lesions involving the posterior visual pathways, affecting the lateral parietal-temporal-occipital cortex and the underlying white matter (as shown by magnetic resonance imaging stud...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523800000444
更新日期:1990-10-01 00:00:00
abstract::Ultrastructural examination of photoreceptor inner segment ellipsoids in larval (4, 8, and 15 days postfertilization; dpf) and adult zebrafish identified morphologically different types of mitochondria. All photoreceptors had mitochondria of different sizes (large and small). At 4 dpf, rods had small, moderately stain...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/S095252381300059X
更新日期:2014-01-01 00:00:00
abstract::In the present work, we explore the perceptual bases of infants' spontaneous looking preferences among isoluminant chromatic stimuli (Bornstein, 1975). Three experiments were conducted. In Experiment 1, adult subjects made brightness matches between a white standard and each of six isoluminant chromatic stimuli. The c...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523804213360
更新日期:2004-05-01 00:00:00
abstract::Dopaminergic interplexiform cells in the retina of the blue acara were investigated using an antiserum against tyrosine hydroxylase and PAP visualization. In whole-mount preparations, we observed a homogeneous distribution of cell bodies throughout the retina without any indication of regional specialization. At the f...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523800010737
更新日期:1992-09-01 00:00:00
abstract::The purpose of the present study was to compare standard multifocal visual evoked potential (mfVEP) pattern-reversal responses with those produced by pattern-onset, pattern-offset, and pulsed pattern stimuli. mfVEP recordings were obtained from five normal subjects using VERIS and a 4-electrode array. The standard rev...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/S0952523808080954
更新日期:2009-03-01 00:00:00
abstract::We used qualitative tests to assess the sensitivity of 1043 V2 neurons (predominantly multiunits) in anesthetised macaque monkeys to direction, length, orientation, and color of moving bar stimuli. Spectral sensitivity was additionally tested by noting ON or OFF responses to flashed stimuli of varied size and color. T...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523802191164
更新日期:2002-03-01 00:00:00
abstract::Contrast adaptation occurs in both the retina and the cortex. Defining its spatial dependence is crucial for understanding its potential roles. We thus asked to what degree contrast adaptation depends on spatial frequency, including cross-adaptation. Measuring the pattern electroretinogram (PERG) and the visual evoked...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523802195095
更新日期:2002-09-01 00:00:00
abstract::Neurons in the superficial layers of the midbrain superior colliculus (SC) exhibit distinct tuning properties for visual stimuli, but, unlike neurons in the geniculocortical visual pathway, most respond best to visual stimuli that are smaller than the classical receptive field (RF). The mechanism underlying this size ...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/S0952523806230062
更新日期:2006-09-01 00:00:00
abstract::The entire population of ganglion cells in the retina of the toad Bufo marinus was labeled by retrograde transport of a lysine-fixable biotinylated dextran amine of 3000 molecular weight. Synaptic connections between bipolar, amacrine, and ganglion cells in the inner plexiform layer were quantitatively analyzed, with ...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523800011792
更新日期:1997-11-01 00:00:00
abstract::There are four cone morphologies in zebrafish, corresponding to UV (U), blue (B), green (G), and red (R)-sensing types; yet genetically, eight cone opsins are expressed. How eight opsins are physiologically siloed in four cone types is not well understood, and in larvae, cone physiological spectral peaks are unstudied...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/S0952523819000075
更新日期:2019-07-30 00:00:00
abstract::We have developed two brain slice preparations for studying tectofugal visual pathways in the chick: conventional, 400-microns slices ("thin slices"), and "thick slices" which encompass the rostral pole of the optic tectum and the contralateral optic nerve. Stimulation was delivered with a bipolar electrode positioned...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523800008622
更新日期:1996-07-01 00:00:00
abstract::Two groups of retinal cone bipolar cells (CBCs) in rats were found to express voltage-gated Na+ channels. The axon terminals of the first group stratify in sublamina 2 of the inner plexiform layer (IPL) and partially overlap with the OFF-cholinergic band. This group was identified as type 3 CBCs. The axon terminals of...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/S0952523808080851
更新日期:2008-09-01 00:00:00
abstract::The topographical distributions of the relative ratio of long- (L) and middle- (M) wavelength sensitive cone opsin messenger RNA (mRNA) in human and baboon retinas were mapped using real-time polymerase chain reaction. The L:M mRNA ratio increased in a central-to-peripheral gradient in both species, being quite pronou...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/S095252380623325X
更新日期:2006-05-01 00:00:00
abstract::The phosphoinositide (PI) intracellular signaling pathway, which triggers Ca2+ release from intracellular stores, appears to be a central feature of phototransduction in most invertebrate species studied. Procedures designed to inhibit PI-pathway reactions cause suppression of excitation to dim lights. However, in Lim...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523898151076
更新日期:1998-01-01 00:00:00
abstract::The distribution of GABA-like immunoreactivity in the cat retina was studied through the use of preembedding immunocytochemistry for light microscopy and by postembedding immunogold techniques for electron microscopy. Staining was observed in both inner and outer plexiform layers. Approximately 30% of the somata in th...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523800012323
更新日期:1989-01-01 00:00:00
abstract::In birds, neurons of the isthmo-optic nucleus (ION), as well as "ectopic" neurons, send axons to the retina, where they synapse on cells in the inner nuclear layer (INL). Previous work has shown that centrifugal axons can be divided into two anatomically distinct types depending on their model of termination: either "...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523800001747
更新日期:1994-03-01 00:00:00
abstract::Surround enhancement (sensitization) is a poorly understood form of network adaptation in which the kinetics of the responses of retinal neurons to test stimuli become faster, and absolute sensitivity of the responses increases with increasing level of steady, surrounding light. Surround enhancement has been observed ...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523800006751
更新日期:1995-11-01 00:00:00
abstract::Color vision impairment was examined in patients with type 2 diabetes mellitus (DM2) without retinopathy. We assessed the type and degree of distortions of individual color spaces. DM2 patients (n = 32), and age-matched controls (n = 20) were tested using the Farnsworth D-15 and the Lanthony D-15d tests. In addition, ...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/S0952523806233546
更新日期:2006-05-01 00:00:00
abstract::Recently, we introduced a phototransduction model that was able to account for the reproducibility of vertebrate rod single-photon responses (SPRs) (Hamer et al., 2003). The model was able to reproduce SPR statistics by means of stochastic activation and inactivation of rhodopsin (R*), transducin (G alpha ), and phosp...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/S0952523805224045
更新日期:2005-07-01 00:00:00
abstract::The retinas of adult teleost fish can regenerate following injury, but little is known about the neuronal integration of the visual scene that is performed by the regenerated retina. Using goldfish retinal ganglion cells (RGCs) as the experimental system, an evaluation of dendritic arbor structure and passive electrot...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523899162060
更新日期:1999-03-01 00:00:00
abstract::Nucleus rotundus and nucleus dorsolateralis posterior (DLP) are the thalamic components of two parallel pathways within the tectofugal division of the pigeon visual system. An earlier study (Hodos, Weiss & Bessette, 1986) had shown that lesions in direct telencephalic recipients of projections from rotundus and DLP pr...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523800001036
更新日期:1988-01-01 00:00:00
abstract::The inhibition of [3H]acetylcholine (ACh) release from cholinergic amacrine cells by glycine and GABA was studied using an in vivo eyecup preparation in anesthetized rabbits. Glycine (1 mM) had no effect on basal ACh release, but completely blocked the light-evoked release of ACh. Glycine also blocked the strong poten...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523898156067
更新日期:1998-11-01 00:00:00
abstract::Starburst amacrine cells (SACs), the only acetylcholine (ACh)-releasing amacrine cells (ACs) in adult rabbit retina, contain GABA and are key elements in the retina's directionally selective (DS) mechanism. Unlike many other GABAergic ACs, they use glutamic acid decarboxlyase (GAD)(67), not GAD(65), to synthesize GABA...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/S0952523810000052
更新日期:2010-03-01 00:00:00
abstract::Lesion or inactivation of the superior colliculus (SC) of the cat results in an animal that fails to orient toward peripheral visual stimuli which normally evoke a brisk, reflexive orienting response. A failure to orient toward a visual stimulus could be the result of a sensory impairment (a failure to detect the visu...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s095252380320609x
更新日期:2003-11-01 00:00:00
abstract::In the arthropod medulla, which is the second ganglion on the afferent visual pathway, a column of about 40 cells represents each point in space (i.e. compound eye facet). Some stages of visual processing underlying the responses of one class of cells in the locust medulla have been identified. These transient cells g...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523800004831
更新日期:1991-10-01 00:00:00
abstract::The peripheral visual field is marked by a deterioration in color sensitivity, sometimes attributed to the random wiring of midget bipolar cells to cone photoreceptors in the peripheral retina (Mullen, 1991; Mullen & Kingdom, 1996). Using psychophysical methods, we explored differences in the sensitivity of peripheral...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523803205058
更新日期:2003-09-01 00:00:00
abstract::In previous experiments we established that a light flash reduced cGMP levels of toad rod outer segments within the transduction time interval, but that recovery of the dark level of cGMP occurred more slowly than reported electrophysiological recovery of membrane potential. We now report that a second light flash acc...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/s0952523800003230
更新日期:1993-01-01 00:00:00
abstract::Natural scenes contain a variety of visual cues that facilitate boundary perception (e.g., luminance, contrast, and texture). Here we explore whether single neurons in early visual cortex can process both contrast and texture cues. We recorded neural responses in cat A18 to both illusory contours formed by abutting gr...
journal_title:Visual neuroscience
pub_type: 杂志文章
doi:10.1017/S0952523807070113
更新日期:2007-01-01 00:00:00