Browsing by Subject "Optic nerve damage"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Open Access
    MicroRNA regulation in an animal model of acute ocular hypertension
    (John Wiley & Sons Ltd., 2017-02-01) Wang, Jiawei; Valiente Soriano, Francisco Javier; Nadal-Nicolás, Francisco Manuel; Rovere, Giuseppe; Chen, Shida; Huang, Wenbin; Agudo Barriuso, Marta; Jonas, Jost B.; Vidal Sanz, Manuel; Zhang, Xiulan; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Medicina
    Purpose: To analyse miRNA regulation in a rat model of acute ocularhypertension (AOH). Methods: Acute ocular hypertension (AOH) was induced in the left eye of adult albino rats by inserting a cannula connected with a saline container into the anterior chamber. The contralateral eye served as a control. Seven days later, animals were killed. Retinas were used either for quantitative analysis of retinal ganglion cells (RGCs) and microglial cells or for miRNA array hybridization, qRT-PCR and Western blotting. Results: Anatomically, AOH caused axonal degeneration, a significant loss of RGCs and a significant increase in microglial cells in the ganglion cell layer. The miRNAs microarray analysis revealed 31 differentially expressed miRNAs in the AOH versus control group, and the regulation of 12 selected microRNAs was further confirmed by qRT-PCR. Bioinformatic analysis indicates that several signalling pathways are putatively regulated by the validated miRNAs. Of particular interest was the inflammatory pathway signalled by mitogen-activated protein kinases (MAPKs). In agreement with the in silico analysis, p38 MAP kinase, tumour necrosis factor-alpha (TNF-a) and iNOS proteins were significantly upregulated in the AOH retinas. Conclusions: Acute IOP elevation led to changes in the expression of miRNAs, whose target genes were associated with the regulation of microglia-mediated neuroinflammation or neural apoptosis. Addressing miRNAs in the process of retinal ischaemia and optic nerve damage in association with high IOP elevation may open new avenues in preventing retinal ganglion cell apoptosis and may serve as target for future therapeutic regimen in acute ocular hypertension and retinal ischaemic conditions.
  • Thumbnail Image
    Publication
    Open Access
    Understanding glaucomatous damage: Anatomical and functional data from ocular hypertensive rodent retinas
    (Elsevier, 2012-01-27) Miralles de Imperial, Jaime; Vidal Sanz, Manuel; Salinas Navarro, Manuel Ángel; Nadal-Nicolás, Francisco Manuel; Valiente Soriano, Francisco Javier; Agudo Barriuso, Marta; Villegas Pérez, Maria Paz; Avilés Trigueros, Marcelino; Alarcón Martínez, Luis; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
    Glaucoma, the second most common cause of blindness, is characterized by a progressive loss of retinal ganglion cells and their axons, with a concomitant loss of the visual field. Although the exact pathogenesis of glaucoma is not completely understood, a critical risk factor is the elevation, above normal values, of the intraocular pressure. Consequently, deciphering the anatomical and functional changes occurring in the rodent retina as a result of ocular hypertension has potential value, as it may help elucidate the pathology of retinal ganglion cell degeneration induced by glaucoma in humans. This paper predominantly reviews the cumulative information from our laboratory’s previous, recent and ongoing studies, and discusses the deleterious anatomical and functional effects of ocular hypertension on retinal ganglion cells (RGCs) in adult rodents. In adult rats and mice, perilimbar and episcleral vein photocauterization induces ocular hypertension, which in turn results in devastating damage of the RGC population. In wide triangular sectors, preferentially located in the dorsal retina, RGCs lose their retrograde axonal transport, first by a functional impairment and after by mechanical causes. This axonal damageaffects up to 80% of the RGC population, and eventuallycauses their death, with somal and intraretinal axonal degeneration that resembles that observed after optic nerve crush. Importantly, while ocular hypertension affects the RGC population, it spares non-RGC neurons located in the ganglion cell layer of the retina. In addition, functional and morphological studies show permanent alterations of the inner and outer retinal layers, indicating that further to a crush-like injury of axon bundles in the optic nerve head there may by additional insults to the retina, perhaps of ischemic nature.