The retina of the PCD/PCD mouse as a model of photoreceptor degeneration. A structural and functional study

Marchena, Miguel; Lara, Juan M.; Aijón, José; Germain, Francisco; Villa, Pedro de la; Velasco, Almudena

doi:10.1016/j.exer.2011.07.010

Cited by 18 publications

(26 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Using a qualitative approach, these studies reported that the expression pattern of these synaptic proteins is preserved even at an advanced stage of retinal degeneration, suggesting that second and third-order retinal neurons can transmit visual information synaptically. One of these reports, although it did not quantitate, reported upregulation of synapsin in the IPL of PCD mouse [38] (see their Fig. 7C,D), which is consistent with our results for synapsin-I.…”

Section: Discussionsupporting

confidence: 92%

“…Synaptic proteins, including the ones examined here, have been studied in a variety of animal models of photoreceptor degeneration [8], [37]–[38]. Using a qualitative approach, these studies reported that the expression pattern of these synaptic proteins is preserved even at an advanced stage of retinal degeneration, suggesting that second and third-order retinal neurons can transmit visual information synaptically.…”

Section: Discussionmentioning

confidence: 85%

See 1 more Smart Citation

Loss of Photoreceptors Results in Upregulation of Synaptic Proteins in Bipolar Cells and Amacrine Cells

et al. 2014

View full text Add to dashboard Cite

Deafferentation is known to cause significant changes in the postsynaptic neurons in the central nervous system. Loss of photoreceptors, for instance, results in remarkable morphological and physiological changes in bipolar cells and horizontal cells. Retinal ganglion cells (RGCs), which send visual information to the brain, are relatively preserved, but show aberrant firing patterns, including spontaneous bursts of spikes in the absence of photoreceptors. To understand how loss of photoreceptors affects the circuitry presynaptic to the ganglion cells, we measured specific synaptic proteins in two mouse models of retinal degeneration. We found that despite the nearly total loss of photoreceptors, the synaptophysin protein and mRNA levels in retina were largely unaltered. Interestingly, the levels of synaptophysin in the inner plexiform layer (IPL) were higher, implying that photoreceptor loss results in increased synaptophysin in bipolar and/or amacrine cells. The levels of SV2B, a synaptic protein expressed by photoreceptors and bipolar cells, were reduced in whole retina, but increased in the IPL of rd1 mouse. Similarly, the levels of syntaxin-I and synapsin-I, synaptic proteins expressed selectively by amacrine cells, were higher after loss of photoreceptors. The upregulation of syntaxin-I was evident as early as one day after the onset of photoreceptor loss, suggesting that it did not require any massive or structural remodeling, and therefore is possibly reversible. Together, these data show that loss of photoreceptors results in increased synaptic protein levels in bipolar and amacrine cells. Combined with previous reports of increased excitatory and inhibitory synaptic currents in RGCs, these results provide clues to understand the mechanism underlying the aberrant spiking in RGCs.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 85%

Loss of Photoreceptors Results in Upregulation of Synaptic Proteins in Bipolar Cells and Amacrine Cells

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Our findings support a role of TTLL10 as a polyglycylase on co-expression with TTLL3 as reported by Ikegami et al in cell lines through co-transfection experiments. In mice with a variant of the deglutamylase CCP1, an increase in polyglutamylation results in the degeneration of photoreceptors in the retina (39). A series of human mutations in the deglutamylase CCP5 have been reported in patients with visual impairments (40,41).…”

Section: Discussionmentioning

confidence: 99%

Post-translational polymodification of β1 tubulin regulates motor protein localisation in platelet production and function

Khan

Slater

Maclachlan

et al. 2019

Preprint

View full text Add to dashboard Cite

Key Points 1• The platelet specific -1 tubulin (encoded by TUBB1) is polyglutamylated and polyglycylated in platelet producing iPSC-2 derived megakaryocytes (MKs). 3 • The platelet marginal band is polyglutamylated upon activation. 4 • Polymodification in both MKs and platelets impact motor protein localisation. 5• Patients with C-terminal TUBB1 variants demonstrate macrothrombocytopenia, and the CRISPR mediated knock out of 6 TUBB1 in iPSC-MKs results in a complete loss of proplatelet production. 7• 3 unrelated families with mutations in TTLL10 report moderate to severe bleeding and increased mean platelet volume 8 (MPV), suggesting polyglycylation through TTLL10 is required for healthy platelet production. 9• A system of reversible polymodifications mediated through the graded expression of modifying enzymes (TTLLs and 10 CCPs) throughout MK maturation is required for proplatelet formation and subsequent platelet function. 11 Introduction 12Microtubules are large, cytoskeletal filaments vital to a host of critical functions including cell division, signalling, cargo 13 transport, motility, and function(1-3). Despite their ubiquitous expression and high structural conservation, microtubules also 14 drive unique morphologies and functions in specialist cell types like ciliated cells, spermatozoa, and neurons (4, 5). The question 15 of how filaments expressed in every cell in the body can facilitate complex and highly unique behaviours like neurotransmitter 16 release and retinal organisation has been addressed by the tubulin code. This is a paradigm which accounts for the specialisation 17 of microtubules and their organisation by describing a mechanism in which particular cells express lineage restricted isoforms 18 of tubulin. These cell specific isoforms are then subject to a series of post-translational modifications which alter the mechanical 19 properties of microtubules, and their capacity to recruit accessory proteins (e.g. motor proteins) (1)(2)(3) 5). 20 A host of tubulin post-translational modifications (PTMs) have been reported in a range of cell types, including (but not limited 21 to) tyrosination, acetylation, glutamylation, glycylation, and phosphorylation. In recent years links between the loss of specific 22 tubulin PTMs, either through the aberrant expression of tubulin isoforms or the loss of effecting or reversing enzymes, has 23 emerged (5). The loss of post-translationally modified tubulin has been reported to impact motile and non-motile ciliary 24 function (including respiratory cilia, retinal cells), spermatogenesis, muscular disorders, and neurological development and 25 function (1,(5)(6)(7)(8)(9)(10)(11). Of the many cell systems in which careful regulation of tubulin modification is required for healthy function, 26 the role of the tubulin code in the generation of blood platelets from their progenitors, megakaryocytes (MKs) remains relatively 27 poorly understood. 28 Platelets are the smallest component of peripheral blood, and circulate as anucleate cells with ...

show abstract

“…En la retina, Islet1 se expresa principalmente en células ganglionares, y de hecho se utiliza como marcador de dichas células en el pollo (Austin et al, 1995) y en ratón (Marchena et al, 2011). Se ha descrito que Islet1 está implicado en la diferenciación de células amacrinas colinérgicas de rata (Galli-Resta et al, 1997) y de ratón (Elshatory et al, 2007b), y en bipolares ON de ratón (Elshatory et al, 2007b) y de humanos (Haverkamp et al, 2003).…”

Section: Islet1unclassified

“…Islet1 se expresa en células ganglionares maduras de pez cebra , carpín (Sánchez-González, 2009), tenca (Bejarano-Escobar et al, 2009), pollo (Austin et al, 1995), rata (Thor et al, 1991;Galli-Resta et al, 1997); ratón (Elshatory et al, 2007a;Marchena et al, 2011) y cerdo (Guduric-Fuchs et al, 2009. Islet1 se empieza a detectar en las células ganglionares de la retina desde las primeras etapas del desarrollo, y es un gen clave en la diferenciación de dichas células en pez cebra (Masai et al, 2000;Shkumatava y Neumann, 2005;Huang et al, 2009), tortuga (Francisco-Morcillo et al, 2006, pollo (Díaz et al, 2000;Sakagami et al, 2003;Boije et al, 2008), ratón (Elshatory et al, 2007a;Pan et al, 2008;Sun et al, 2009;Prasov y Glaser, 2012) y cerdo (Guduric-Fuchs et al, 2009).…”

Section: Expresión De Islet1 En La Retina Adultaunclassified

Caracterización de los progenitores neurales de retina adulta del pez cebra

Gutiérrez¹

View full text Add to dashboard Cite

Cuando emprendas tu viaje haciaÍtaca debes rogar que el viaje sea largo, lleno de peripecias, lleno de experiencias... I IIEste trabajo ha sido posible gracias a la ayuda directa o indirecta de muchas personas.Al Prof. Dr. José Aijón por haber permitido mi integración en el grupo de trabajo que dirige, y haberme sugerido el tema de investigación.A mis directores de la tesis, la Dra. Rosario Arévalo y el Prof. Dr. Juan Lara, por el apoyo mostrado durante estos años, por las sugerencias y correcciones. Gracias por la confianza depositada en mi trabajo A la Dra. Concepción Lillo, a la Dra. Almudena Velasco y al Dr.Ángel Porteros, por compartir sus conocimientos, que en gran medida han mejorado este trabajo.Al grupo del Dr. Chichung Lie, porque además de llevarme a la Oktoberfest me enseñaron todo acerca de los cultivos de neuroesferas. En especial a Tobi, por su paciencia y su confianza en mi.Al laboratorio de la Dra. Laure Bally-Cuif, especialmente a Jakob, por hacerme ver que el pez cebra es algo más que la retina.A la Dra. Rosario Sánchez. Ella me enseñó todo lo que sabía, y yo he seguido lo mejor que he podido su camino. A ver hasta donde llega.A la Dra. Henrike Scholz, con la que aprendí mucho acerca del cerebro, ya que gracias a la pasión que me transmitió por la neurociencia empecé y termino esta Tesis Doctoral.A mis compañeros del INCyL. A Miguel y Saúl, que llevamos ya unos cuantos años juntos, por todas las experiencias compartidas, las buenas y las no tan buenas. A Marta, que aunque ahora anda por las Alemanias, me ha echado una mano siempre que ha podido. A Fernando, por hacer del día a día del laboratorio algo interesante. A Bego, por las comidas compartidas, por los desahogos y las risas. A Hector, Antonio, Rafa, Marcelo, Laura, porque sin todos vosotros esto no sería lo mismo.A los compañeros del comité de Intermón Oxfam de Salamanca, por hacerme creer que un mundo más justo es posible. A los que están y los que han pasado por aquí, que son muchos. Unas gracias especiales a Ximena, Carlos, Mercedes, Ana, Sofía, Marta, Carmen y Mar (por dos).A los de Würzburg, a Ebru, Laura, Mar, Grigorios, Jose y Alejandro por haber hecho de la estancia alemana una de las mejores experiencias.A la cuadri, porque aun sin entenderme, han estado ahí para charlar y compartir. En especial a Ainara y Maite, por todo lo que hemos pasado juntas y todo lo que nos queda. III La retina de teleósteosEl ojo es elórgano encargado de la visión (Fig. 1.1). Las capas externas del ojo son la esclera y la coroides por la parte posterior, y la córnea por la parte delantera. Dentro del globo ocular se diferencian dos cámaras: la cámara anterior, que contiene el humor acuoso, y la cámara posterior, con el humor vítreo. Estas dos cámaras están separadas por el cristalino y el iris. Figura 1.1: Esquema del globo ocular humano (Kolb et al., 2000)

show abstract

The retina of the PCD/PCD mouse as a model of photoreceptor degeneration. A structural and functional study

Cited by 18 publications

References 41 publications

Loss of Photoreceptors Results in Upregulation of Synaptic Proteins in Bipolar Cells and Amacrine Cells

Loss of Photoreceptors Results in Upregulation of Synaptic Proteins in Bipolar Cells and Amacrine Cells

Post-translational polymodification of β1 tubulin regulates motor protein localisation in platelet production and function

Caracterización de los progenitores neurales de retina adulta del pez cebra

Contact Info

Product

Resources

About