Browsing by Subject "Optic nerve"

Now showing 1 - 9 of 9
  • Thumbnail Image
    Publication
    Open Access
    Absence of galectin-3 promotes neuroprotection in retinal ganglion cells after optic nerve injury
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Abreu, Carla Andreia; De Lima, Silmara Veline; Mendonça, Henrique Rocha; Oliveira Goulart, Camila de; Blanco Martinez, Ana Maria
    A trauma to the mature central nervous system (CNS) often leads to persistent deficits, due to the inability of axons to regenerate after being injured. Increasing evidence suggests that pro-inflammatory and pro-apoptotic genes can present a major obstacle to promoting neuroprotection of retinal ganglion cells and consequently succeed in axonal regeneration. This study evaluated the effect of the absence of galectin-3 (Gal-3) on retinal ganglion cells (RGC) survival and axonal regeneration/degeneration after optic nerve crush injury. Two weeks after crush there was a 2.6 fold increase in the rate of cell survival in Gal-3-/- mice (1283±79.15) compared to WT animals (495.4±53.96). However, no regeneration was observed in the Gal-3-/- mice two weeks after lesion. Furthermore, axonal degeneration presented a particular pattern on those mice; Electron Microscopy (EM) analysis showed incomplete axon degeneration while the WT mice presented an advanced stage of degeneration. This suggests that the removal of the nerve fibers in the Gal 3-/- mice could be deficient and this would cause a delay in the process of Wallerian degeneration once there is a decrease in the number of macrophages/microglia in the nerve. This study demonstrates how the absence of Gal-3 can affect RGC survival and optic nerve regeneration/degeneration after lesion. Our results suggest that the absence of Gal-3 plays an important role in the survival of RGC and thus can be a potential target for therapeutic intervention in RGC neuroprotection.
  • Thumbnail Image
    Publication
    Restricted
    Axotomy-induced retinal ganglion cell death in adult mice: quantitative and topographic time course analyses
    (Elsevier, 2011-02-24) Galindo Romero, Caridad; Avilés Trigueros, Marcelino; Jiménez López, Manuel; Valiente Soriano, Francisco Javier; Salinas Navarro, Manuel Ángel; Nadal-Nicolás, Francisco Manuel; Villegas Pérez, Maria Paz; Vidal Sanz, Manuel; Agudo Barriuso, Marta; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Anatomía Humana y Psicobiología; Facultades de la UMU::Facultad de Medicina
    The fate of retinal ganglion cells after optic nerve injury has been thoroughly described in rat, but not in mice, despite the fact that this species is amply used as a model to study different experimental paradigms that affect retinal ganglion cell population. Here we have analyzed, quantitatively and topographically, the course of mice retinal ganglion cells loss induced by intraorbital nerve transection. To do this, we have doubly identified retinal ganglion cells in all retinas by tracing them from their main retinorecipient area, the superior colliculi, and by their expression of BRN3A (product of Pou4f1 gene). In rat, this transcription factor is expressed by a majority of retinal ganglion cells; however in mice it is not known how many out of the whole population of these neurons express it. Thus, in this work we have assessed, as well, the total population of BRN3A positive retinal ganglion cells. These were automatically quantified in all whole-mounted retinas using a newly developed routine. In control retinas, tracedretinal ganglion cells were automatically quantified, using the previously reported method (SalinasNavarro et al., 2009b). After optic nerve injury, though, traced-retinal ganglion cells had to be manually quantified by retinal sampling and their total population was afterwards inferred. In naïve whole-mounts, the mean ( standard deviation) total number of traced-retinal ganglion cells was 40,437 ( 3196) andofBRN3Apositive ones was 34,697( 1821). Retinal ganglion cell loss was first significant for both markers 5 days post-axotomy and by day 21, the last time point analyzed, only 15% or 12% of traced or BRN3A positive retinal ganglion cells respectively, survived. Isodensity maps showed that, in control retinas, BRN3A and traced-retinal ganglion cells were distributed similarly, being densest in the dorsal retina along the naso-temporal axis. After axotomy the progressive loss of BRN3A positive retinal ganglion cells was diffuse and affected the entire retina. In conclusion, this is the first study assessing the values, in terms of total number and density, of the retinal ganglion cells surviving axotomy from 2 till 21 days post-lesion. Besides, we have demonstrated that BRN3A is expressed by 85.6% of the total retinal ganglion cell population, and because BRN3A positive retinal ganglion cells show the same spatial distribution and temporal course of degeneration than traced ones, BRN3A is a reliable marker to identify, quantify and assess, ex-vivo, retinal ganglion cell loss in this species.
  • Thumbnail Image
    Publication
    Open Access
    Differential expression of calretinin in the developing and regenerating zebrafish visual system
    (Murcia : F. Hernández, 2004) García-Crespo, D.; Vecino, E.
    Calretinin is a calcium-binding protein which participates in a variety of functions including calcium buffering and neuronal protection. It also serves as a developmental marker of retinal ganglion cells (RGCs). In order to study the role of calretinin in the development and regeneration of RGCs, we have studied its pattern of expression in the retina at different developmental stages, as well as during optic nerve regeneration by means of immunohistochemistry. During development, calretinin is found for the first time in RGCs when they connect with the optic tectum. Optic nerves from adult zebrafish were crushed and after different survival times, calretinin expression in the retina, optic nerve tract and optic tectum was studied. From the day of crushing to 10 days later, calretinin expression was found to be downregulated within RGCs and their axons, as was also observed during the early developmental stages of RGCs, when they are not committed to a definite cell phenotype. Moreover, 13 days after lesion, when the regenerating axons arrived at the optic tectum, a recovery of calretinin immunoreactivity within the RGCs was observed. These results indicate that calretinin may play an important role during optic nerve regeneration, Thus, the downregulation of Calretinin during the growth of the RGC axons towards the target during development as well as during their regeneration after injury, indicates that an increase the availability of cytosolic calcium is integral to axon outgrowth thus recapitulating the pattern observed during development.
  • Thumbnail Image
    Publication
    Open Access
    Marcadores de imagen retinianos estructurales y vasculares en el trastorno de déficit de atención e hiperactividad (TDAH)
    (Universidad de Murcia, 2025-03-12) Miquel López, Carmen; García Medina, José Javier; Río Vellosillo, Mónica del; Escuela Internacional de Doctorado
    El Trastorno por Déficit de Atención e Hiperactividad (TDAH) es un trastorno neuropsiquiátrico prevalente en la infancia, afectando al 5-7% de los niños. Debido a su impacto significativo, resulta fundamental mejorar las estrategias diagnósticas. Dado que la retina es una extensión del sistema nervioso central, ofrece una oportunidad para su estudio, permitiendo un análisis no invasivo mediante técnicas como la tomografía de coherencia óptica (OCT) y la angiografía por tomografía de coherencia óptica (OCTA). Estas técnicas pueden ser útiles para evaluar el TDAH sin recurrir a la neuroimagen cerebral tradicional. El objetivo de este estudio es identificar parámetros estructurales y vasculares retinianos en pacientes con TDAH utilizando OCT y OCTA, con la esperanza de facilitar un diagnóstico más preciso y rápido. Se trata de un estudio prospectivo, caso-control, que incluyó a 50 pacientes diagnosticados con TDAH y 50 controles normotípicos. Las mediciones incluyeron el grosor total de la retina y sus capas (internas, externas, capa de células ganglionares, fibras nerviosas maculares y papilares), así como parámetros vasculares como la densidad y perfusión vascular, tanto en la mácula como en el nervio óptico. Los resultados muestran que los pacientes con TDAH presentan una disminución significativa del grosor total de la retina, especialmente en las capas externas. Aunque las células ganglionares también tendían a disminuir, esto fue más evidente en las fibras nerviosas maculares, particularmente en los ojos izquierdos. Además, se observó una reducción del grosor en las combinaciones de capas (CCG+mRNFL y CCG+mRNFL+OR). Las curvas ROC indicaron un poder discriminativo bajo-moderado para el grosor total (0,6-0,7) y un poder moderado (>0,7) para las capas externas. En el análisis del nervio óptico, se detectó una disminución significativa en la capa de fibras nerviosas peripapilares, notablemente en el sector correspondiente a las VII horas. No obstante, los hallazgos de la OCTA en cuanto a la densidad y perfusión vascular en la mácula y el nervio óptico no alcanzaron significación estadística, ni se encontraron diferencias en la zona avascular foveal. En conclusión, los pacientes con TDAH presentan diferencias estructurales y vasculares en la retina al compararlos con sujetos normotípicos. Aunque algunas de estas diferencias alcanzan un grado moderado de discriminación, estos hallazgos podrían ser útiles para mejorar el diagnóstico de este trastorno en el futuro.  
  • Thumbnail Image
    Publication
    Open Access
    Neurotrophins in the developing and regenerating visual system
    (Murcia : F. Hernández, 1998) von Bartheld, C.S.
    The neurotrophins NGF, BDNF, NT-3 and NT-4 have a wide range of effects in the development and regeneration of neural circuits in the visual system of vertebrates. This review focuses on the localization and functions of neurotrophins in the retina, lateral geniculate nucleus, suprachiasmatic nucleus, superior colliculus/optic tectum, and isthmic nuclei. Research of the past 20 years has shown that neurotrophins and their receptors are localized in numerous visual centers from the retina to the visual cortex, and that neurotrophins influence proliferation, neurite outgrowth and survival of cells in the visual system in vitro and in vivo. A relationship between electrical activity and neurotrophic functions has been established in several visual centers in the CNS, and neurotrophins have been implicated in synaptic plasticity in the visual cortex. Besides functions of neurotrophins as retrograde, target-derived trophic factors, recent data indicate that neurotrophins may have anterograde, afferent as well as local, paracrine actions in the retina, optic nerve and the visual cortex. Some neurotrophins appear to regulate proliferation and survival of glial cells in the optic pathways. Neurotrophins increase the survival of retinal ganglion cells after axotomy or ischemia and they promote the regeneration of retinal ganglion cell axons in some vertebrates. Neurotrophins also rescue photoreceptors from degeneration. These findings implicate the neurotrophins not only as important regulators during development, but also as potential therapeutic agents in degenerative retinal diseases and after optic nerve injury.
  • Thumbnail Image
    Publication
    Open Access
    Restorative potential of ciliary body cells in a retinal ganglion cell degeneration model
    (Nature Research, 2025-05-03) Fernández-Nogales, Marta; Herrera, Macarena; Herrera, Eloisa ; Lucas Ruiz, Fernando; Valiente Soriano, Francisco Javier; Nadal-Nicolás, Francisco Manuel; Agudo Barriuso, Marta; Lucas Ruiz, Fernando; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
    The ciliary body (CB) has been proposed as a niche of neural stem cells because, in vitro, cells from this area are able to form neurospheres, proliferate and differentiate. Here, we explore the potential of CB cells to differentiate and replace degenerated retinal ganglion cells (RGCs) in vivo. CB cells and cells from the subventricular zone (SVZ) were isolated from adult or postnatal C57BL/6Tg(CAG-EGFP) mice, respectively, and intravitreally injected into intact retinas, immediately after optic nerve crush or 45 days after the lesion of adult C57/BL/6 mice. Retinas were analysed in whole mounts or cross sections at different time points. Controls were matched untreated retinas. Neither cell type caused gliosis or toxicity when injected into intact retinas. When CB or SVZ cells were injected right after axotomy, they formed an epimembrane without integrating in the retina. However, when CB cells were administered in retinas depleted of RGCs, they integrated into the ganglion cell layer and expressed RGC and neuronal markers. Although SVZ cells were also able to integrate into RGC depleted retinas they did so more slowly than CB cells. These results shed light in the long-standing question of whether cells in the CB have the potential to transdifferentiate in vivo and point to the CB as a suitable source of cells that could be used in cell-replacement therapies for neurodegenerative diseases of the retina.
  • Thumbnail Image
    Publication
    Open Access
    Transient Downregulation of Melanopsin Expression After Retrograde Tracing or Optic Nerve Injury in Adult Rats
    (Association for Research in Vision and Ophthalmology., 2015-07-01) Nadal-Nicolás, Francisco Manuel; Madeira, Maria H.; Salinas Navarro, Manuel Ángel; Jiménez López, Manuel; Galindo Romero, Caridad; Ortín Martínez, Arturo; Santiago, Ana Raquel; Vidal Sanz, Manuel; Agudo Barriuso, Marta; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
    PURPOSE. To investigate the effect of retrograde tracing or axotomy on melanopsin mRNA expression and immunodetection in albino and pigmented rat retinas. METHODS. Groups were (1) intact-na¨ıve retinas; (2) optic nerve crush (ONC) analyzed at 7 days (7d) or 2 months (2m); (3) Fluorogold (FG) tracing from the superior colliculi (SCi) analyzed at 7d or 2m; (4) tracing from the intact optic nerve (ON) with FG or hydroxystilbamidine methanesulfonate (OHSt), analyzed 3d later; and (5) sham tracing from the ON or sham surgery. Brn3a and melanopsin were double stained in whole mounts to quantify and assess the distribution of orthotopic and displaced Brn3aþ retinal ganglion cells (Brn3aþRGCs) and melanopsinþRGCs (mþRGCs). Freshly dissected retinas were used for melanopsin mRNA quantitative PCR. RESULTS. Tracing from the SCi did not affect the number of Brn3aþRGCs or mþRGCs counted in pigmented rats. However, only 55% of mþRGCs were immunodetected in albinos at 7d, although by 2m the mþRGCs counts returned to normal. Optic nerve tracing had a more dramatic effect (38% or 77% of mþRGCs were immunodetected in albino or pigmented rats) that occurred irrespectively of the tracer (OHSt or FG). This effect was not observed in the sham groups. After ONC, Brn3aþRGCs decreased to 37% and 8% by 7d and 2m, respectively. Melanopsin þRGC counts diminished to 30% at 7d, but recovered to 49% of controls by 2m. Melanopsin mRNA was downregulated after ON tracing or 7d after ONC, but did not differ from intact values 2m after ONC. CONCLUSIONS. Following ON injury or retrograde tracing there is a transient melanopsin downregulation that should be taken into account when assessing mþRGC survival.
  • Thumbnail Image
    Publication
    Open Access
    Ultrastructural study of the neuroglial and macrophagic reaction in Wallerian degeneration of the adult rat optic nerve
    (Murcia : F. Hernández, 1991) Carbonell, A.L.; Boya, J.; Calvo, J.L.; Marín, J.F.
    The Wallerian degeneration of the optic nerve of adult rat has been studied after destroying the retina. Animals were sacrificed between 4 days and 1 year after the lesion. Different cell types of the optic nerve have been studied ultrastructurally. Our results demonstrate the existence of a population of macrophages, probably of microglial origin, responsible for scavenging degenerated myelin. Astrocytes suffer a process of proliferation and hypertrophy. and are massively stuffed by gliofilaments, leading to a glial scar. These cells apparently do not participate in phagocytic phenomena, while some cytoplasmic inclusions (e.g. lipid droplets) suggest some implication in the local metabolization of some tissue degradation products. Oligodendrocytes do not undergo ultrastructural changes, showing a rather quiescent appearance.
  • Thumbnail Image
    Publication
    Open Access
    Visual deficits and diagnostic and therapeutic strategies for neurofibromatosis type 1: bridging science and patient-centered care
    (MDPI, 2024-05-09) Miyagishima, Kiyoharu J.; Qiao, Fengyu; Stasheff, Steven F.; Nadal-Nicolás, Francisco Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Óptica y Optometría
    Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder primarily affecting children and adolescents characterized by multisystemic clinical manifestations. Mutations in neurofibromin, the protein encoded by the Nf1 tumor suppressor gene, result in dysregulation of the RAS/MAPK pathway leading to uncontrolled cell growth and migration. Neurofibromin is highly expressed in several cell lineages including melanocytes, glial cells, neurons, and Schwann cells. Individuals with NF1 possess a genetic predisposition to central nervous system neoplasms, particularly gliomas affecting the visual pathway, known as optic pathway gliomas (OPGs). While OPGs are typically asymptomatic and benign, they can induce visual impairment in some patients. This review provides insight into the spectrum and visual outcomes of NF1, current diagnostic techniques and therapeutic interventions, and explores the influence of NF1-OPGS on visual abnormalities. We focus on recent advancements in preclinical animal models to elucidate the underlying mechanisms of NF1 pathology and therapies targeting NF1-OPGs. Overall, our review highlights the involvement of retinal ganglion cell dysfunction and degeneration in NF1 disease, and the need for further research to transform scientific laboratory discoveries to improved patient outcomes.