van Versendaal D.,Institute of Visual Arts |
Rajendran R.,Institute of Visual Arts |
Saiepour M.,Institute of Visual Arts |
Klooster J.,Retinal Sciences |
And 7 more authors.
Neuron | Year: 2012
During development, cortical plasticity is associated with the rearrangement of excitatory connections. While these connections become more stable with age, plasticity can still be induced in the adult cortex. Here we provide evidence that structural plasticity of inhibitory synapses onto pyramidal neurons is a major component of plasticity in the adult neocortex. In vivo two-photon imaging was used to monitor the formation and elimination of fluorescently labeled inhibitory structures on pyramidal neurons. We find that ocular dominance plasticity in the adult visual cortex is associated with rapid inhibitory synapse loss, especially of those present on dendritic spines. This occurs not only with monocular deprivation but also with subsequent restoration of binocular vision. We propose that in the adult visual cortex the experience-induced loss of inhibition may effectively strengthen specific visual inputs with limited need for rearranging the excitatory circuitry. van Versendaal et al. show that plasticity in the adult visual cortex is associated with the rapid loss of inhibitory synapses. This may represent a mechanism allowing adult plasticity to occur without the need for extensive reorganization of excitatory synapses. © 2012 Elsevier Inc.
Dudok J.J.,Royal Netherlands Academy of Arts and science |
Sanz A.S.,Royal Netherlands Academy of Arts and science |
Lundvig D.M.S.,Royal Netherlands Academy of Arts and science |
Sothilingam V.,University of Tübingen |
And 4 more authors.
GLIA | Year: 2013
MPP3 and CRB1 both interact directly with PALS1/MPP5 and through this scaffold protein may form a large protein complex. To investigate the role of MPP3 in the retina we have analyzed conditional mutant Mpp3 knockout mice. Ultrastructural localization studies revealed that MPP3 is predominantly localized in apical villi of Müller glia cells. Retinas lacking MPP3 developed late onset retinal degeneration, with sporadic foci of rosette formation in the central part of the retina. Retinal degeneration in Mpp3 cKO mice was accelerated by exposure to moderate levels of white light. Electroretinography recordings in aging mice under both scotopic and photopic conditions ranged from normal to mildly subnormal, while the magnitude correlated with the strength and extent of morphological alterations. Loss of MPP3 resulted in significant loss of PALS1 at the subapical region adjacent to adherens junctions, and loss of MPP3 in Pals1 conditional knockdown retinas significantly accelerated the onset of retinal degeneration. These data suggest that MPP3 is required for maintaining proper levels of PALS1 at the subapical region, and indicate that the MPP3 gene is a candidate modulator of the Crumbs complex. © 2013 Wiley Periodicals, Inc.
Park B.,Royal Netherlands Academy of Arts and science |
Alves C.H.,Royal Netherlands Academy of Arts and science |
Lundvig D.M.,Royal Netherlands Academy of Arts and science |
Tanimoto N.,University of Tübingen |
And 10 more authors.
Journal of Neuroscience | Year: 2011
The membrane-associated palmitoylated protein 5 (MPP5 or PALS1) is thought to organize intracellular PALS1-CRB-MUPP1 protein scaffolds in the retina that are involved in maintenance of photoreceptor-Müller glia cell adhesion. In humans, the Crumbs homolog 1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there is no clear genotype-phenotype correlation for CRB1 mutations, which suggests that other components of the CRB complex may influence the severity of retinal disease. Therefore, to understand the physiological role of the Crumbs complex proteins, especially PALS1, we generated and analyzed conditional knockdown mice for Pals1. Small irregularly shaped spots were detected throughout the PALS1 deficient retina by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. The electroretinography a-and b-wave was severely attenuated in the aged mutant retinas, suggesting progressive degeneration of photoreceptors. The histological analysis showed abnormal retinal pigment epithelium structure, ectopic photoreceptor nuclei in the subretinal space, an irregular outer limiting membrane, half rosettes of photoreceptors in the outer plexiform layer, and a thinner photoreceptor synaptic layer suggesting improper photoreceptor cell layering during retinal development. The PALS1 deficient retinas showed reduced levels of Crumbs complex proteins adjacent to adherens junctions, upregulation of glial fibrillary acidic protein indicative of gliosis, and persisting programmed cell death after retinal maturation. The phenotype suggests important functions of PALS1 in the retinal pigment epithelium in addition to the neural retina. © 2011 the authors.
van Tijn P.,Royal Netherlands Academy of Arts and science |
van Tijn P.,Hubrecht Institute for Developmental Biology and Stem Cell Research |
Sizarov A.,Heart Failure Research Center |
Kamermans M.,Retinal Sciences |
And 2 more authors.
Human Molecular Genetics | Year: 2011
Pontocerebellar hypoplasia (PCH) represents a group (PCH1-6) of neurodegenerative autosomal recessive disorders characterized by hypoplasia and/or atrophy of the cerebellum, hypoplasia of the ventral pons, progressive microcephaly and variable neocortical atrophy. The majority of PCH2 and PCH4 cases are caused by mutations in the TSEN54 gene; one of the four subunits comprising the tRNA-splicing endonuclease (TSEN) complex. We hypothesized that TSEN54 mutations act through a loss of function mechanism. At 8 weeks of gestation, human TSEN54 is expressed ubiquitously in the brain, yet strong expression is seen within the telencephalon and metencephalon. Comparable expression patterns for tsen54 are observed in zebrafish embryos. Morpholino (MO) knockdown of tsen54 in zebrafish embryos results in loss of structural definition in the brain. This phenotype was partially rescued by co-injecting the MO with human TSEN54 mRNA. A developmental patterning defect was not associated with tsen54 knockdown; however, an increase in cell death within the brain was observed, thus bearing resemblance to PCH pathophysiology. Additionally, N-methyl-N-nitrosourea mutant zebrafish homozygous for a tsen54 premature stop-codon mutation die within 9 days post-fertilization. To determine whether a common disease pathway exists between TSEN54 and other PCH-related genes, we also monitored the effects of mitochondrial arginyl-tRNA synthetase (rars2; PCH1 and PCH6) knockdown in zebrafish. Comparable brain phenotypes were observed following the inhibition of both genes. These data strongly support the hypothesis that TSEN54 mutations cause PCH through a loss of function mechanism. Also we suggest that a common disease pathway may exist between TSEN54-and RARS2-related PCH, which may involve a tRNA processing-related mechanism. © The Author 2011. Published by Oxford University Press. All rights reserved.
Abedi G.,Retinal Sciences |
Patal P.,Boston University |
Doros G.,Boston University |
Subramanian M.L.,Boston University
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2011
Background: The purpose of this paper is to study the differences between central subfield macular thickness (CSMT) measurements obtained by time-domain Stratus optical coherence tomography (OCT) and Cirrus spectral domain OCT (Carl Zeiss Meditec, Dublin, CA) and to formulate an equation to convert CSMT values from one to the other. Methods: CSMT were measured by both Stratus Macula OCT and Cirrus Macula OCT in 46 healthy subjects. Agreement between measurements was calculated using Lin's concordance coefficient. Results: The average age of our group was 30 with the logMAR visual acuity of -0.015. The Stratus CSMT measurement (mean ± standard deviation) 193.91 ± 21.7 was statistically significant from the Cirrus CSMT measurement 252.82 ± 28.4 (p < 0.001). The transformation equation 0.76×-0.51 from Cirrus to Stratus resulted in values that best agreed with the observed Stratus OCT values. Conclusions: We identified a significant difference of CSMT measurements between Stratus and Cirrus. The Cirrus typically gave a higher value of CSMT. We derived a linear equation to convert the measurements from Cirrus to Stratus which resulted in transformed values that concord with the observed Stratus OCT values. © 2011 Springer-Verlag.
Simon S.,Retinal Sciences |
Athanasiov P.A.,Retinal Sciences |
Jain R.,Retinal Sciences |
Raymond G.,Retinal Sciences |
Gilhotra J.S.,Retinal Sciences
Indian Journal of Ophthalmology | Year: 2012
A 29-year-old lady receiving repeated blood transfusions for β thalassemia since childhood, presented with rapidly deteriorating symptoms of night blindness and peripheral visual field loss. She was recently commenced on high-dose intravenous desferrioxamine for reducing the systemic iron overload. Clinical and investigative findings were consistent with desferrioxamine-related pigmentary retinopathy and optic neuropathy. Recovery was partial following cessation of desferrioxamine. This report highlights the ocular side-effects of desferrioxamine mesylate and the need to be vigilant in patients on high doses of desferrioxamine.
Retinal Sciences | Date: 2016-03-08
Retinal Sciences | Date: 2016-03-08
Retinal Sciences | Date: 2016-03-08