View More View Less
  • 1 University of Pécs Department of Experimental Zoology and Neurobiology, Faculty of Sciences Ifjúság útja 6 H-7624 Pécs Hungary
  • 2 PTE-MTA “Lendület” PACAP Research Team Department of Anatomy Pécs Hungary
  • 3 The Scripps Research Institute La Jolla CA USA
  • 4 University of Wisconsin-Madison Department of Psychiatry Madison WI USA
  • 5 University of Pécs Department of Sportbiology Pécs Hungary
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $752.00

Urocortin 2 (Ucn 2) is a corticotrop releasing factor paralog peptide with many physiological functions and it has widespread distribution. There are some data on the cytoprotective effects of Ucn 2, but less is known about its neuro- and retinoprotective actions. We have previously shown that Ucn 2 is protective in ischemia-induced retinal degeneration. The aim of the present study was to examine the protective potential of Ucn 2 in monosodium-glutamate (MSG)-induced retinal degeneration by routine histology and to investigate cell-type specific effects by immunohistochemistry. Rat pups received MSG applied on postnatal days 1, 5 and 9 and Ucn 2 was injected intravitreally into one eye. Retinas were processed for histology and immunocytochemistry after 3 weeks. Immunolabeling was determined for glial fibrillary acidic protein, vesicular glutamate transporter 1, protein kinase Cα, calbindin, parvalbumin and calretinin. Retinal tissue from animals treated with MSG showed severe degeneration compared to normal retinas, but intravitreal Ucn 2 treatment resulted in a retained retinal structure both at histological and neurochemical levels: distinct inner retinal layers and rescued inner retinal cells (different types of amacrine and rod bipolar cells) could be observed. These findings support the neuroprotective function of Ucn 2 in MSG-induced retinal degeneration.

  • Atlasz T, Babai N, Reglodi D, Kiss P, Tamas A, Bari F, Domoki F, Gabriel R: Diazoxide is protective in the rat retina against ischemic injury induced by bilateral carotid occlusion and glutamate-induced degeneration. Neurotox. Res. 12, 105–111 (2007)

    Gabriel R , 'Diazoxide is protective in the rat retina against ischemic injury induced by bilateral carotid occlusion and glutamate-induced degeneration ' (2007 ) 12 Neurotox. Res. : 105 -111.

    • Search Google Scholar
  • Atlasz T, Szabadfi K, Kiss P, Babai N, Koszegi Z, Tamas A, Reglodi D, Gabriel R: PACAP-mediated neuroprotection of neurochemically identified cell types in MSG-induced retinal degeneration. J. Mol. Neurosci. 36, 97–104 (2008)

    Gabriel R , 'PACAP-mediated neuroprotection of neurochemically identified cell types in MSG-induced retinal degeneration ' (2008 ) 36 J. Mol. Neurosci. : 97 -104.

    • Search Google Scholar
  • Atlasz T: Analysis of the effects of different neuroprotective compounds in retinal degeneration models in rats. PhD thesis. University of Pécs (2008)

    Atlasz T , '', in Analysis of the effects of different neuroprotective compounds in retinal degeneration models in rats , (2008 ) -.

  • Atlasz T, Szabadfi K, Reglodi D, Kiss P, Tamas A, Toth G, Molnar A, Szabo K, Gabriel R: Effects of pituitary adenylate cyclase activating polypeptide and its fragments on retinal degeneration induced by neonatal monosodium glutamate treatment. Ann. N.Y. Acad. Sci. 1163, 348–352 (2009)

    Gabriel R , 'Effects of pituitary adenylate cyclase activating polypeptide and its fragments on retinal degeneration induced by neonatal monosodium glutamate treatment ' (2009 ) 1163 Ann. N.Y. Acad. Sci. : 348 -352.

    • Search Google Scholar
  • Atlasz T, Szabadfi K, Kiss P, Racz B, Gallyas F, Tamas A, Gaal V, Marton Z, Gabriel R, Reglodi D: Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects. Ann. N.Y. Acad. Sci. 1200, 128–139, Review (2010)

    Reglodi D , 'Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects ' (2010 ) 1200 Ann. N.Y. Acad. Sci. : 128 -139.

    • Search Google Scholar
  • Babai N, Atlasz T, Tamas A, Reglodi D, Toth G, Kiss P, Gabriel R: Degree of damage compensation by various PACAP treatments in monosodium glutamate-induced retinal degeneration. Neurotox. Res. 8, 227–233 (2005)

    Gabriel R , 'Degree of damage compensation by various PACAP treatments in monosodium glutamate-induced retinal degeneration ' (2005 ) 8 Neurotox. Res. : 227 -233.

    • Search Google Scholar
  • Babai N, Atlasz T, Tamas A, Reglodi D, Toth G, Kiss P, Gabriel R: Search for the optimal monosodium glutamate treatment schedule to study the neuroprotective effects of PACAP in the retina. Ann. N.Y. Acad. Sci. 1070, 149–155 (2006)

    Gabriel R , 'Search for the optimal monosodium glutamate treatment schedule to study the neuroprotective effects of PACAP in the retina ' (2006 ) 1070 Ann. N.Y. Acad. Sci. : 149 -155.

    • Search Google Scholar
  • Chambille I, Serviere J: Neurotoxic effects of neonatal injections of monosodium L-glutamate (L-MSG) on the retinal ganglion cell layer of the golden hamster: anatomical and functional consequences on the circadian system. J. Comp. Neurol. 338, 67–82 (1993)

    Serviere J , 'Neurotoxic effects of neonatal injections of monosodium L-glutamate (L-MSG) on the retinal ganglion cell layer of the golden hamster: anatomical and functional consequences on the circadian system ' (1993 ) 338 J. Comp. Neurol. : 67 -82.

    • Search Google Scholar
  • Choi JS, Pham TT, Jang YJ, Bui BC, Lee BH, Joo KM, Cha CI, Lee KH: Corticotropin-releasing factor (CRF) and urocortin promote the survival of cultured cerebellar GABAergic neurons through the type 1 CRF receptor. J. Kor. Med. Sci. 21, 518–526 (2006)

    Lee KH , 'Corticotropin-releasing factor (CRF) and urocortin promote the survival of cultured cerebellar GABAergic neurons through the type 1 CRF receptor ' (2006 ) 21 J. Kor. Med. Sci. : 518 -526.

    • Search Google Scholar
  • Dautzenberg FM, Huber G, Higelin J, Py-Lang G, Kilpatrick GJ: Evidence for the abundant expression of arginine 185 containing human CRF2 receptors and the role of position 185 for receptor-ligand selectivity. Neuropharmacology 39, 1368–1376 (2000)

    Kilpatrick GJ , 'Evidence for the abundant expression of arginine 185 containing human CRF2 receptors and the role of position 185 for receptor-ligand selectivity ' (2000 ) 39 Neuropharmacology : 1368 -1376.

    • Search Google Scholar
  • Dautzenberg FM, Hauger RL: The CRF peptide family and their receptors: yet more partners discovered. Trends Pharmacol. Sci. 23, 71–77 (2002)

    Hauger RL , 'The CRF peptide family and their receptors: yet more partners discovered ' (2002 ) 23 Trends Pharmacol. Sci. : 71 -77.

    • Search Google Scholar
  • Eng LF, Smith ME, De Vellis J, Skoff RP: Recent studies on the glial fibrillary acidic protein. Ann. N.Y. Acad. Sci. 455, 525–537 (1985)

    Skoff RP , 'Recent studies on the glial fibrillary acidic protein ' (1985 ) 455 Ann. N.Y. Acad. Sci. : 525 -537.

    • Search Google Scholar
  • Facci L, Stevens DL, Pangallo M, Franceschini D, Skaper SD, Strijbos PJLM: Corticotropin-releasing factor (CRF) and related peptides confer neuroprotection via type 1 CRF receptors. Neuropharmacology 45, 623–636 (2003)

    Strijbos PJLM , 'Corticotropin-releasing factor (CRF) and related peptides confer neuroprotection via type 1 CRF receptors ' (2003 ) 45 Neuropharmacology : 623 -636.

    • Search Google Scholar
  • Fekete EM, Zorrilla EP: Physiology, pharmacology and therapeutic relevance of urocortins in mammals: Ancient CRF paralogs. Frontiens in Neuroendocrinol. 28, 1–27 (2007)

    Zorrilla EP , 'Physiology, pharmacology and therapeutic relevance of urocortins in mammals: Ancient CRF paralogs ' (2007 ) 28 Frontiens in Neuroendocrinol : 1 -27.

    • Search Google Scholar
  • Gong J, Jellali A, Mutterer J, Sahel JA, Rendon A, Picaud S: Distribution of vesicular glutamate transporters in rat and human retina. Brain Res. 1082, 73–85 (2006)

    Picaud S , 'Distribution of vesicular glutamate transporters in rat and human retina ' (2006 ) 1082 Brain Res. : 73 -85.

    • Search Google Scholar
  • Hamano K, Kiyama H, Emson PC, Manabe R, Nakauchi M, Tohyama M: Localization of two calcium binding proteins, calbindin (28 kD) and parvalbumin (12 kD), in the vertebrate retina. J. Comp. Neurol. 302, 417–424 (1990)

    Tohyama M , 'Localization of two calcium binding proteins, calbindin (28 kD) and parvalbumin (12 kD), in the vertebrate retina ' (1990 ) 302 J. Comp. Neurol. : 417 -424.

    • Search Google Scholar
  • Hwang IK, Yoo KY, Kim DS, Jung JY, Shin MC, Seo K, Kim KS, Kang TC, Won MH: Comparative study on calretinin immunoreactivity in gerbil and rat retina. Anat. Histol. Embryol. 34, 129–131 (2005)

    Won MH , 'Comparative study on calretinin immunoreactivity in gerbil and rat retina ' (2005 ) 34 Anat. Histol. Embryol. : 129 -131.

    • Search Google Scholar
  • Lopez-Perez SJ, Ureña-Guerrero ME, Morales-Villagran A: Monosodium glutamate neonatal treatment as a seizure and excitotoxic model. Brain Res. 1317, 246–256 (2010)

    Morales-Villagran A , 'Monosodium glutamate neonatal treatment as a seizure and excitotoxic model ' (2010 ) 1317 Brain Res. : 246 -256.

    • Search Google Scholar
  • Osborne NN, Casson RJ, Wood JP, Chidlow G, Graham M, Melena J: Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog. Retin. Eye Res. 23, 91–147, Review (2004)

    Melena J , 'Retinal ischemia: mechanisms of damage and potential therapeutic strategies ' (2004 ) 23 Prog. Retin. Eye Res. : 91 -147.

    • Search Google Scholar
  • Osborne M, Weber K: Cell-type specific markers in differentiation and pathology. Cell 31, 303 (1982)

    Weber K , 'Cell-type specific markers in differentiation and pathology ' (1982 ) 31 Cell : 303 -.

    • Search Google Scholar
  • Pan W, Kastin AJ: Urocortin and the brain. Prog. Neurobiol. 84, 148–156 (2008)

    Kastin AJ , 'Urocortin and the brain ' (2008 ) 84 Prog. Neurobiol. : 148 -156.

  • Pedersen WA, Wan R, Zhang P, Mattson MP: Urocortin, but not urocortin II, protects cultured hippocampal neurons from oxidative and excitotoxic cell death via corticotropin-releasing hormone receptor type I. J. Neurosci. 22, 404–412 (2002)

    Mattson MP , 'Urocortin, but not urocortin II, protects cultured hippocampal neurons from oxidative and excitotoxic cell death via corticotropin-releasing hormone receptor type I ' (2002 ) 22 J. Neurosci. : 404 -412.

    • Search Google Scholar
  • Racz B, Gallyas F Jr, Kiss P, Toth G, Hegyi O, Gasz B, Borsiczky B, Ferencz A, Roth E, Tamas A, Lengvari I, Lubics A, Reglodi D: The neuroprotective effects of PACAP in monosodium glutamate-induced retinal lesion involve inhibition of proapoptotic signaling pathways. Regul. Pept. 137, 20–26 (2006)

    Reglodi D , 'The neuroprotective effects of PACAP in monosodium glutamate-induced retinal lesion involve inhibition of proapoptotic signaling pathways ' (2006 ) 137 Regul. Pept. : 20 -26.

    • Search Google Scholar
  • Racz B, Tamas A, Kiss P, Toth G, Gasz B, Borsiczky B, Ferencz A, Gallyas F Jr, Roth E, Reglodi D: Involvement of ERK and CREB signaling pathways in the protective effect of PACAP in monosodium glutamate-induced retinal lesion. Ann. N.Y. Acad. Sci. 1070, 507–511 (2006)

    Reglodi D , 'Involvement of ERK and CREB signaling pathways in the protective effect of PACAP in monosodium glutamate-induced retinal lesion ' (2006 ) 1070 Ann. N.Y. Acad. Sci. : 507 -511.

    • Search Google Scholar
  • Romano C, Price MT, Olney JW: Delayed excitotoxic neurodegeneration induced by excitatory amino acid agonists in isolated retina. J. Neurochem. 65, 59–67 (1995)

    Olney JW , 'Delayed excitotoxic neurodegeneration induced by excitatory amino acid agonists in isolated retina ' (1995 ) 65 J. Neurochem. : 59 -67.

    • Search Google Scholar
  • Schmidt KG, Bergert H, Funk RH: Neurodegenerative diseases of the retina and potential for protection and recovery. Curr. Neuropharmacol. 6, 164–178 (2008)

    Funk RH , 'Neurodegenerative diseases of the retina and potential for protection and recovery ' (2008 ) 6 Curr. Neuropharmacol. : 164 -178.

    • Search Google Scholar
  • Skofitsch G, Jacobowitz DM: Corticotropin releasing factor-like immunoreactive neurons in the rat retina. Brain Res. Bull. 12, 539–542 (1984)

    Jacobowitz DM , 'Corticotropin releasing factor-like immunoreactive neurons in the rat retina ' (1984 ) 12 Brain Res. Bull. : 539 -542.

    • Search Google Scholar
  • Sucher NJ, Lipton SA, Dreyer EB: Molecular basis of glutamate toxicity in retinal ganglion cells. Vision Res. 37, 3483–3493 (1997)

    Dreyer EB , 'Molecular basis of glutamate toxicity in retinal ganglion cells ' (1997 ) 37 Vision Res. : 3483 -3493.

    • Search Google Scholar
  • Sun Q, Ooi VE, Chan SO: N-methyl-D-aspartate-induced excitotoxicity in adult rat retina is antagonized by single systemic injection of MK-801. Exp. Brain Res. 138, 37–45 (2001)

    Chan SO , 'N-methyl-D-aspartate-induced excitotoxicity in adult rat retina is antagonized by single systemic injection of MK-801 ' (2001 ) 138 Exp. Brain Res. : 37 -45.

    • Search Google Scholar
  • Szabadfi K, Atlasz T, Reglodi D, Kiss P, Danyadi B, Fekete EM, Zorrilla EP, Tamas A, Szabo K, Gabriel R: Urocortin 2 protects against retinal degeneration following bilateral common carotid artery occlusion in the rat. Neurosci. Lett. 455, 42–45 (2009)

    Gabriel R , 'Urocortin 2 protects against retinal degeneration following bilateral common carotid artery occlusion in the rat ' (2009 ) 455 Neurosci. Lett. : 42 -45.

    • Search Google Scholar
  • Szabadfi K, Atlasz T, Horvath G, Kiss P, Hamza L, Farkas J, Tamas A, Lubics A, Gabriel R, Reglodi D: Early postnatal enriched environment decreases retinal degeneration induced by monosodium glutamate treatment in rats. Brain Res. 1259, 107–112 (2009)

    Reglodi D , 'Early postnatal enriched environment decreases retinal degeneration induced by monosodium glutamate treatment in rats ' (2009 ) 1259 Brain Res. : 107 -112.

    • Search Google Scholar
  • Tamas A, Gabriel R, Racz B, Denes V, Kiss P, Lubics A, Lengvari I, Reglodi D: Effects of pituitary adenylate cyclase activating polypeptide in retinal degeneration induced by monosodium-glutamate. Neurosci. Lett. 372, 110–113 (2004)

    Reglodi D , 'Effects of pituitary adenylate cyclase activating polypeptide in retinal degeneration induced by monosodium-glutamate ' (2004 ) 372 Neurosci. Lett. : 110 -113.

    • Search Google Scholar
  • Vidal-Sanz M, Lafuente M, Sobrado-Calvo P, Selles-Navarro I, Rodriguez E, Mayor-Torroglosa S, Villegas-Perez MP: Death and neuroprotection of retinal ganglion cells after different types of injury. Neurotox. Res. 2, 215–227 (2000)

    Villegas-Perez MP , 'Death and neuroprotection of retinal ganglion cells after different types of injury ' (2000 ) 2 Neurotox. Res. : 215 -227.

    • Search Google Scholar
  • Wassle H, Yamashita M, Greferath U, Grunert U: The rod bipolar cell of the mammalian retina. Vis. Neurosci. 7, 99–112 (1991)

    Grunert U , 'The rod bipolar cell of the mammalian retina ' (1991 ) 7 Vis. Neurosci. : 99 -112.

    • Search Google Scholar
  • Williamson DE, Eldred WD: Synaptic organization of two types of amacrine cells with CRF-like immunoreactivity in the turtle retina. Vis. Neurosci. 6, 257–269 (1991)

    Eldred WD , 'Synaptic organization of two types of amacrine cells with CRF-like immunoreactivity in the turtle retina ' (1991 ) 6 Vis. Neurosci. : 257 -269.

    • Search Google Scholar
  • Williamson DE, Eldred WD: Amacrine and ganglion cells with corticotrophin releasing-factor like immunoreactivity in the turtle retina. J. Comp. Neurol. 280, 424–435 (1989)

    Eldred WD , 'Amacrine and ganglion cells with corticotrophin releasing-factor like immunoreactivity in the turtle retina ' (1989 ) 280 J. Comp. Neurol. : 424 -435.

    • Search Google Scholar
  • Zhang DR, Gallagher M, Sladek CD, Yeh HH: Postnatal development of corticotrophin releasing factor-like immunoreactive amacrine cells in the rat retina. Brain Res. Dev. Brain Res. 51, 185–194 (1990)

    Yeh HH , 'Postnatal development of corticotrophin releasing factor-like immunoreactive amacrine cells in the rat retina ' (1990 ) 51 Brain Res. Dev. Brain Res. : 185 -194.

    • Search Google Scholar
  • Zhang DR, Yeh HH: Corticotropin releasing factor-like immunoreactivity (CRFLI) in horizontal cells of the developing rat retina. Vis. Neurosci. 6, 383–391 (1991)

    Yeh HH , 'Corticotropin releasing factor-like immunoreactivity (CRFLI) in horizontal cells of the developing rat retina ' (1991 ) 6 Vis. Neurosci. : 383 -391.

    • Search Google Scholar
  • Zhang DR, Yeh HH: Histogenesis of corticotropin releasing factor-like immunoreactive amacrine cells in the rat retina. Brain Res. Dev. Brain Res. 53, 194–199 (1990)

    Yeh HH , 'Histogenesis of corticotropin releasing factor-like immunoreactive amacrine cells in the rat retina ' (1990 ) 53 Brain Res. Dev. Brain Res. : 194 -199.

    • Search Google Scholar
  • Zmijewski MA, Sharma RK, Slominski AT: Expression of molecular equivalent of hypothalamic-pituitary-adrenal axis in adult retinal pigment epithelium. J. Endocrinol. 193, 157–169 (2007)

    Slominski AT , 'Expression of molecular equivalent of hypothalamic-pituitary-adrenal axis in adult retinal pigment epithelium ' (2007 ) 193 J. Endocrinol. : 157 -169.

    • Search Google Scholar

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Nov 2020 0 0 0
Dec 2020 0 0 0
Jan 2021 0 0 0
Feb 2021 0 0 0
Mar 2021 0 0 0
Apr 2021 0 0 0
May 2021 0 0 0