Retinal ischemia: mechanisms of damage and potential therapeutic strategies

Retinal ischemia: mechanisms of damage and potential therapeutic strategies Retinal ischemia is a common cause of visual impairment and blindness. At the cellular level, ischemic retinal injury consists of a self-reinforcing destructive cascade involving neuronal depolarisation, calcium influx and oxidative stress initiated by energy failure and increased glutamatergic stimulation. There is a cell-specific sensitivity to ischemic injury which may reflect variability in the balance of excitatory and inhibitory neurotransmitter receptors on a given cell. A number of animal models and analytical techniques have been used to study retinal ischemia, and an increasing number of treatments have been shown to interrupt the “ischemic cascade” and attenuate the detrimental effects of retinal ischemia. Thus far, however, success in the laboratory has not been translated to the clinic. Difficulties with the route of administration, dosage, and adverse effects may render certain experimental treatments clinically unusable. Furthermore, neuroprotection-based treatment strategies for stroke have so far been disappointing. However, compared to the brain, the retina exhibits a remarkable natural resistance to ischemic injury, which may reflect its peculiar metabolism and unique environment. Given the increasing understanding of the events involved in ischemic neuronal injury it is hoped that clinically effective treatments for retinal ischemia will soon be available. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Progress in Retinal and Eye Research Elsevier

Retinal ischemia: mechanisms of damage and potential therapeutic strategies

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Publisher
Elsevier
Copyright
Copyright © 2003 Elsevier Ltd
ISSN
1350-9462
eISSN
1873-1635
DOI
10.1016/j.preteyeres.2003.12.001
Publisher site
See Article on Publisher Site

Abstract

Retinal ischemia is a common cause of visual impairment and blindness. At the cellular level, ischemic retinal injury consists of a self-reinforcing destructive cascade involving neuronal depolarisation, calcium influx and oxidative stress initiated by energy failure and increased glutamatergic stimulation. There is a cell-specific sensitivity to ischemic injury which may reflect variability in the balance of excitatory and inhibitory neurotransmitter receptors on a given cell. A number of animal models and analytical techniques have been used to study retinal ischemia, and an increasing number of treatments have been shown to interrupt the “ischemic cascade” and attenuate the detrimental effects of retinal ischemia. Thus far, however, success in the laboratory has not been translated to the clinic. Difficulties with the route of administration, dosage, and adverse effects may render certain experimental treatments clinically unusable. Furthermore, neuroprotection-based treatment strategies for stroke have so far been disappointing. However, compared to the brain, the retina exhibits a remarkable natural resistance to ischemic injury, which may reflect its peculiar metabolism and unique environment. Given the increasing understanding of the events involved in ischemic neuronal injury it is hoped that clinically effective treatments for retinal ischemia will soon be available.

Journal

Progress in Retinal and Eye ResearchElsevier

Published: Jan 1, 2004

References

  • Expression of the inducible isoform of nitric oxide synthase in the retinas of human subjects with diabetes mellitus
    Abu El-Asrar, A.M; Desmet, S; Meersschaert, A; Dralands, L; Missotten, L; Geboes, K
  • Inhibition of NMDA receptors and nitric oxide synthase reduces ischemic injury of the retina
    Adachi, K; Fujita, Y; Morizane, C; Akaike, A; Ueda, M; Satoh, M; Masai, H; Kashii, S; Honda, Y
  • Electrogenic uptake of glutamate and aspartate into glial cells isolated from the salamander (Ambystoma) retina
    Barbour, B; Brew, H; Attwell, D
  • Differential perturbation of neuronal and glial glutamate transport systems in retinal ischaemia
    Barnett, N.L; Pow, D.V; Bull, N.D
  • The effects of ifenprodil and eliprodil on voltage-dependent Ca 2+ channels and in gerbil global cerebral ischaemia
    Bath, C.P; Farrell, L.N; Gilmore, J; Ward, M.A; Hicks, C.A; O’Neill, M.J; Bleakman, D
  • Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis
    Benveniste, H; Drejer, J; Schousboe, A; Diemer, N.H
  • Changes in the extracellular levels of glutamate and aspartate during ischemia and hypoglycemia. Effects of hypothermia
    Boris-Moller, F; Wieloch, T
  • Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina
    Brandstatter, J.H; Hartveit, E; Sassoe Pognetto, M; Wassle, H
  • Vitreous levels of vascular endothelial growth factor are not influenced by its serum concentrations in diabetic retinopathy
    Burgos, R; Simo, R; Audi, L; Mateo, C; Mesa, J; Garcia Ramirez, M; Carrascosa, A
  • An investigation into the potential mechanisms underlying the neuroprotective effect of clonidine in the retina
    Chao, H.M; Chidlow, G; Melena, J; Wood, J.P.M; Osborne, N.N
  • Excitotoxic cell death dependent on inhibitory receptor activation
    Chen, Q; Moulder, K; Tenkova, T; Hardy, K; Olney, J.W; Romano, C
  • Nitric oxide synthase expression in the transient ischemic rat retina
    Cheon, E.W; Park, C.H; Kang, S.S; Cho, G.J; Yoo, J.M; Song, J.K; Choi, W.S
  • Rat retinal ganglion cell loss caused by kainate, NMDA and ischemia correlates with a reduction in mRNA and protein of Thy-1 and neurofilament light
    Chidlow, G; Osborne, N.N
  • Glutamate neurotoxicity in cortical cell culture
    Choi, D.W; Maulucci Gedde, M; Kriegstein, A.R
  • Horizontal cells of the rat retina are resistant to degenerative processes induced by ischemia-reperfusion
    Chun, M.H; Kim, I.B; Ju, W.K; Kim, K.Y; Lee, M.Y; Joo, C.K; Chung, J.W
  • Ectocellular CD38-catalyzed synthesis and intracellular Ca 2+ -mobilizing activity of cyclic ADP-ribose
    De Flora, A; Franco, L; Guida, L; Bruzzone, S; Zocchi, E
  • Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro
    Drejer, J; Benveniste, H; Diemer, N.H; Schousboe, A
  • ATP-sensitive potassium channels (K ATP ) in retina
    Ettaiche, M; Heurteaux, C; Blondeau, N; Borsotto, M; Tinel, N; Lazdunski, M
  • Neurochemical consequences of kainate-induced toxicity in brain
    Farooqui, A.A; Yi, O.W; Lu, X.R; Halliwell, B; Horrocks, L.A
  • Ca 2+ influx through glutamate receptor-associated channels in retina cells correlates with neuronal cell death
    Ferreira, I.L; Duarte, C.B; Carvalho, A.P
  • Optic nerve blood-flow abnormalities in glaucoma
    Flammer, J; Orgul, S
  • Purification of a neuroprotective component of Parawixia bistriata spider venom that enhances glutamate uptake
    Fontana, A.C; Guizzo, R; Beleboni, R.A.M; Coimbra, N.C; Amara, S.G; Santos, W.F; Coutinho-Netto, J
  • The importance of sodium for anoxic transmission damage in rat hippocampal slices
    Fried, E; Amorim, P; Chambers, G; Cottrell, J.E; Kass, I.S
  • Immunocytochemical localization of the NMDA-R2A receptor subunit in the cat retina
    Goebel, D.J; Aurelia, J.L; Tai, Q; Jojich, L; Poosch, M.S
  • Protective effects of timolol against the neuronal damage induced by glutamate and ischemia in the rat retina
    Goto, W; Ota, T; Morikawa, N; Otori, Y; Hara, H; Kawazu, K; Miyawaki, N; Tano, Y
  • Calcium influx via L-type voltage-gated channels mediates the delayed, elevated increases in steady-state c-fos mRNA levels in cerebellar granule cells exposed to excitotoxic levels of glutamate
    Griffiths, R; Ritchie, L; Lidwell, K; Grieve, A; Malcolm, C.S; Scott, M; Meredith, C
  • N-methyl-D-aspartate-mediated glutamate toxicity in the developing rabbit retina
    Haberecht, M.F; Mitchell, C.K; Lo, G.J; Redburn, D.A
  • Effect of anoxia on ion distribution in the brain
    Hansen, A.J
  • Efficacy and safety of memantine, an NMDA-type open-channel blocker, for reduction of retinal injury associated with experimental glaucoma in rat and monkey
    Hare, W; WoldeMussie, E; Lai, R; Ton, H; Ruiz, G; Feldmann, B; Wijono, M; Chun, T; Wheeler, L
  • Expression of the mRNA of seven metabotropic glutamate receptors (mGluR1 to 7) in the rat retina. An in situ hybridization study on tissue sections and isolated cells
    Hartveit, E; Brandstatter, J.H; Enz, R; Wassle, H
  • Excitotoxic damage of retinal glial cells depends upon normal neuron-glial interactions
    Heidinger, V; Dreyfus, H; Sahel, J; Christen, Y; Hicks, D
  • The optic nerve head in glaucoma
    Hernandez, M.R
  • A metabotropic glutamate receptor regulates transmitter release from cone presynaptic terminals in carp retinal slices
    Hirasawa, H; Shiells, R; Yamada, M
  • Nitric oxide is involved in sustained and delayed cell death of rat retina following transient ischemia
    Ju, W.K; Kim, K.Y; Park, S.J; Park, D.K; Park, C.B; Oh, S.J; Chung, J.W; Chun, M.H
  • Ca 2+ channel antagonists and neuroprotection from cerebral ischemia
    Kobayashi, T; Mori, Y
  • Calcium-induced mitochondrial swelling and cytochrome c release in the brain
    Kobayashi, T; Kuroda, S; Tada, M; Houkin, K; Iwasaki, Y; Abe, H
  • Hyperthermic pre-conditioning protects retinal neurons from N-methyl-D-aspartate (NMDA)-induced apoptosis in rat
    Kwong, J.M; Lam, T.T; Caprioli, J
  • Cerebral ischemia and trauma-different etiologies yet similar mechanisms
    Leker, R.R; Shohami, E
  • Astrocyte heterogeneity
    Levi, G; Patrizio, M
  • Retinal ischemic preconditioning in the rat
    Li, B; Roth, S
  • A narrow window for rescuing cells by the inhibition of calcium influx and the importance of influx route in rat cortical neuronal cell death induced by glutamate
    Li, J; Kato, K; Ikeda, J; Morita, I; Murota, S
  • To die or not to die for neurons in ischemia, traumatic brain injury and epilepsy
    Liou, A.K; Clark, R.S; Henshall, D.C; Yin, X.M; Chen, J
  • Ischemic cell death in brain neurons
    Lipton, P
  • Neuronal and macrophagic nitric oxide synthase isoforms distribution in normal rat retina
    Lopez-Costa, J.J; Goldstein, J; Saavedra, J.P
  • Metabotropic glutamate receptor-mediated hetero-synaptic interaction of red- and green-cone inputs to LHC of carp retina
    Luo, F.J; Liang, P.J
  • Retinal vascular development and oxygen-induced retinopathy
    Lutty, G.A; McLeod, D.S
  • Transport-mediated release of endogenous glutamate in the vertebrate retina
    Maguire, G; Simko, H; Weinreb, R.N; Ayoub, G
  • Perspectives on spreading depression
    Martins-Ferreira, H; Nedergaard, M; Nicholson, C
  • Structure and function of the NMDA receptor channel
    Mori, H; Mishina, M
  • Mitochondria as target for antiischemic drugs
    Morin, D; Hauet, T; Spedding, M; Tillement, J
  • Effects of intraocular injection of a low concentration of zinc on the rat retina
    Nakamichi, N; Chidlow, G; Osborne, N.N
  • Flupirtine ameliorates ischaemic-like death of rat retinal ganglion cells by preventing calcium influx
    Nash, M.S; Wood, J.P.M; Melena, J; Osborne, N.N
  • Neuroprotective strategies
    Obrenovitch, T.P
  • A rapid redistribution of hydrogen ions is associated with depolarization and repolarization subsequent to cerebral ischemia reperfusion
    Obrenovitch, T.P; Scheller, D; Matsumoto, T; Tegtmeier, F; Holler, M; Symon, L
  • The role of group I and group II metabotropic glutamate receptors in modulation of striatal NMDA and quinolinic acid toxicity
    Orlando, L.R; Alsdorf, S.A; Penney, J.B; Young, A.B
  • Antigens associated with specific retinal cells are affected by ischaemia caused by raised intraocular pressure
    Osborne, N.N; Larsen, A.K
  • The influence of experimental ischaemia on protein kinase c and the Gabaergic system in the rabbit retina
    Osborne, N.N; Wood, J.P.M; Muller, A
  • In vivo and in vitro experiments show that betaxolol is a retinal neuroprotective agent
    Osborne, N.N; Cazevieille, C; Carvalho, A.L; Larsen, A.K; DeSantis, L
  • Photoreceptors are preferentially affected in the rat retina following permanent occlusion of the carotid arteries
    Osborne, N.N; Safa, R; Nash, M.S
  • Neuroprotection in relation to retinal ischemia and relevance to glaucoma
    Osborne, N.N; Ugarte, M; Chao, M; Chidlow, G; Bae, J.H; Wood, J.P.M; Nash, M.S
  • Ganglion cell death in glaucoma
    Osborne, N.N; Wood, J.P.M; Chidlow, G; Bae, J.H; Melena, J; Nash, M.S
  • A hypothesis to explain ganglion cell death caused by vascular insults at the optic nerve head
    Osborne, N.N; Melena, J; Chidlow, G; Wood, J.P.M
  • Growth factors and diabetic retinopathy
    Paques, M; Massin, P; Gaudric, A
  • Role of calcium in neuronal cell injury
    Paschen, W
  • 1-Aminoindan-1,5-dicarboxylic acid and (S)-(+)-2-(3-carboxybicyclo(1.1.1) pentyl)-glycine, two mGlu1 receptor-preferring antagonists, reduce neuronal death in in vitro and in vivo models of cerebral ischaemia
    Pellegrini-Giampietro, D.E; Cozzi, A; Peruginelli, F; Leonardi, P; Meli, E; Pellicciari, R; Moroni, F
  • Lactate as a pivotal element in neuron–glia metabolic cooperation
    Pellerin, L
  • Distribution of GABA immunoreactivity in kainic acid-treated rabbit retina
    Perez, M.T; Davanger, S
  • White matter ischaemia
    Petty, M.A; Wettstein, J.G
  • Salvaging the ischaemic penumbra
    Phan, T.G; Wright, P.M; Markus, R; Howells, D.W; Davis, S.M; Donnan, G.A
  • Signalling pathways regulating inducible nitric oxide synthase expression in human kidney epithelial cells
    Poljakovic, M; Nygren, J.M; Persson, K
  • An in vitro rabbit retina model to study electrophysiologic and metabolic function during and following ischemia
    Quinones Hinojosa, A; Ames, A; Malek, J.Y; Maynard, K.I
  • Retinal ischemia leads to apoptosis which is ameliorated by aurintricarboxylic acid
    Rosenbaum, D.M; Rosenbaum, P.S; Gupta, A; Michaelson, M.D; Hall, D.H; Kessler, J.A
  • Measurement of purine nucleoside concentration in the intact rat retina
    Roth, S; Osinski, J.V; Park, S.S; Ostwald, P; Moshfeghi, A.A
  • Retinas from albino rats are more susceptible to ischaemic damage than age-matched pigmented animals
    Safa, R; Osborne, N.N
  • Late preconditioning in rat retina
    Sakamoto, K; Kuwagata, M; Nakahara, T; Ishii, K
  • Interleukin-6 in retinal ischemia reperfusion injury in rats
    Sanchez, R.N; Chan, C.K; Garg, S; Kwong, J.M; Wong, M.J; Sadun, A.A; Lam, T.T
  • Specific physiological roles of cytosolic phospholipase A 2 as defined by gene knockouts
    Sapirstein, A; Bonventre, J.V
  • Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death
    Sattler, R; Tymianski, M
  • Blockade of lactate transport exacerbates delayed neuronal damage in a rat model of cerebral ischemia
    Schurr, A; Payne, R.S; Miller, J.J; Tseng, M.T; Rigor, B.M
  • Increased glutamate uptake and glutamine synthetase activity in neuronal cell cultures surviving chronic hypoxia
    Sher, P.K; Hu, S.X
  • In situ localization of neuronal nitric oxide synthase (nNOS) mRNA in the rat retina
    Shin, D.H; Lee, H.Y; Kim, H.J; Lee, E; Lee, K.H; Lee, W.J; Cho, S.S; Baik, S.H
  • Experimental carotid occlusion
    Spertus, A.D; Slakter, J.S; Weissman, S.S; Henkind, P
  • Mechanisms of photoreceptor death and survival in mammalian retina
    Stone, J; Maslim, J; Valter Kocsi, K; Mervin, K; Bowers, F; Chu, Y; Barnett, N; Provis, J; Lewis, G
  • Antagonists for group I mGluRs attenuate excitotoxic neuronal death in cortical cultures
    Strasser, U; Lobner, D; Behrens, M.M; Canzoniero, L.M; Choi, D.W
  • Tertiary and quaternary local anesthetics protect CNS white matter from anoxic injury at concentrations that do not block excitability
    Stys, P.K; Ransom, B.R; Waxman, S.G
  • Molecular basis of glutamate toxicity in retinal ganglion cells
    Sucher, N.J; Lipton, S.A; Dreyer, E.B
  • Antioxidant properties of calcium dobesilate in ischemic/reperfused diabetic rat retina
    Szabo, M.E; Haines, D; Garay, E; Chiavaroli, C; Farine, J.C; Hannaert, P; Berta, A; Garay, R.P
  • Experimental bilateral carotid artery occlusion
    Takamatsu, J; Hirano, A; Levy, D; Henkind, P
  • Glutamate receptors and circuits in the vertebrate retina
    Thoreson, W.B; Witkovsky, P
  • The nutritive function of glia is regulated by signals released by neurons
    Tsacopoulos, M; Poitry Yamate, C.L; Poitry, S; Perrottet, P; Veuthey, A.L
  • Trafficking of molecules and metabolic signals in the retina
    Tsacopoulos, M; Poitry Yamate, C.L; MacLeish, P.R; Poitry, S
  • Direct evidence for calcium-induced ischemic and reperfusion injury
    Uematsu, D; Greenberg, J.H; Reivich, M; Hickey, W.F
  • Calcium-induced calcium release in neurones
    Verkhratsky, A; Shmigol, A
  • Harnessing the response to tissue hypoxia
    Vincent, K.A; Feron, O; Kelly, R.A
  • Oscillatory potentials in the retina
    Wachtmeister, L
  • Axonal damage and demyelination in the white matter after chronic cerebral hypoperfusion in the rat
    Wakita, H; Tomimoto, H; Akiguchi, I; Matsuo, A; Lin, J.X; Ihara, M; McGeer, P.L
  • Involvement of inflammatory cytokines in central nervous system injury
    Wang, C.X; Shuaib, A
  • Vitamin B6 protects primate retinal neurons from ischemic injury
    Wang, X.D; Kashii, S; Zhao, L; Tonchev, A.B; Katsuki, H; Akaike, A; Honda, Y; Yamashita, J; Yamashima, T
  • Vascular endothelial growth factors and angiogenesis in eye disease
    Witmer, A.N; Vrensen, G.F; Van Noorden, C.J; Schlingemann, R.O
  • Topiramate reduces excitotoxic and ischemic injury in the rat retina
    Yoneda, S; Tanaka, E; Goto, W; Ota, T; Hara, H
  • Excitatory amino acid-induced toxicity in chick retina
    Zeevalk, G.D; Hyndman, A.G; Nicklas, W.J

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