Genomes and Genes
optic nerve injuries
Summary: Injuries to the optic nerve induced by a trauma to the face or head. These may occur with closed or penetrating injuries. Relatively minor compression of the superior aspect of orbit may also result in trauma to the optic nerve. Clinical manifestations may include visual loss, PAPILLEDEMA, and an afferent pupillary defect.
- Tura A, Schuettauf F, Monnier P, Bartz Schmidt K, Henke Fahle S. Efficacy of Rho-kinase inhibition in promoting cell survival and reducing reactive gliosis in the rodent retina. Invest Ophthalmol Vis Sci. 2009;50:452-61 pubmed publisher..These results demonstrate the neuroprotective effect of H-1152P-mediated ROCK-inhibition on retinal cells under stress, which may rely partly on the attenuation of glial cell reactivity. ..
- Ma K, Xu L, Zhang H, Zhang S, Pu M, Jonas J. Effect of brimonidine on retinal ganglion cell survival in an optic nerve crush model. Am J Ophthalmol. 2009;147:326-31 pubmed publisher..Intraperitoneal injections of brimonidine given prophylactically prior to and posttreatment daily after an experimental and standardized optic nerve crush in rats were associated with a higher survival rate of retinal ganglion cells. ..
- Feng D, Chen E, Li X, Liu Y, Wang Y. Standardizing optic nerve crushes with an aneurysm clip. Neurol Res. 2010;32:476-81 pubmed publisher..The present findings suggest that Yasargil aneurysm clip effectively produces permanent injury to the optic nerve with evidence from retrograde tracing of RGCs and may provide a standard technique for optic nerve crush studies. ..
- Smith P, Sun F, Park K, Cai B, Wang C, Kuwako K, et al. SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron. 2009;64:617-23 pubmed publisher..Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury. ..
- Fu Q, Hu B, Wu W, Pepinsky R, Mi S, So K. Blocking LINGO-1 function promotes retinal ganglion cell survival following ocular hypertension and optic nerve transection. Invest Ophthalmol Vis Sci. 2008;49:975-85 pubmed publisher..They also delineated the RhoA and PI-3K/Akt pathways as the predominant mediator of LINGO-1-Fc neuroprotection in this paradigm of RGC death. ..
- de Lima S, Habboub G, Benowitz L. Combinatorial therapy stimulates long-distance regeneration, target reinnervation, and partial recovery of vision after optic nerve injury in mice. Int Rev Neurobiol. 2012;106:153-72 pubmed publisher..Although these methods cannot be applied in the clinic, they point to strategies that might be. ..
- de Lima S, Koriyama Y, Kurimoto T, Oliveira J, Yin Y, Li Y, et al. Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors. Proc Natl Acad Sci U S A. 2012;109:9149-54 pubmed publisher..Regeneration partially restores the optomotor response, depth perception, and circadian photoentrainment, demonstrating the feasibility of reconstructing central circuitry for vision after optic nerve damage in mature mammals. ..
- Templeton J, Nassr M, Vazquez Chona F, Freeman Anderson N, Orr W, Williams R, et al. Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush. BMC Neurosci. 2009;10:90 pubmed publisher..These results form the basis for our continuing interest in the modifiers of retinal injury. ..
- Nadal Nicolás F, Jiménez López M, Sobrado Calvo P, Nieto López L, Cánovas Martínez I, Salinas Navarro M, et al. Brn3a as a marker of retinal ganglion cells: qualitative and quantitative time course studies in naive and optic nerve-injured retinas. Invest Ophthalmol Vis Sci. 2009;50:3860-8 pubmed publisher..Brn3a can be used as a reliable, efficient ex vivo marker to identify and quantify RGCs in control and optic nerve-injured retinas. ..
- Leibinger M, Müller A, Andreadaki A, Hauk T, Kirsch M, Fischer D. Neuroprotective and axon growth-promoting effects following inflammatory stimulation on mature retinal ganglion cells in mice depend on ciliary neurotrophic factor and leukemia inhibitory factor. J Neurosci. 2009;29:14334-41 pubmed publisher..These data confirm a key role for CNTF in directly mediating the neuroprotective and axon regenerative effects of inflammatory stimulation in the eye and identify LIF as an additional contributing factor. ..
- Vessani R, Cunha L, Monteiro M. Progressive macular thinning after indirect traumatic optic neuropathy documented by optical coherence tomography. Br J Ophthalmol. 2007;91:697-8 pubmed
- Leung C, Lindsey J, Crowston J, Lijia C, Chiang S, Weinreb R. Longitudinal profile of retinal ganglion cell damage after optic nerve crush with blue-light confocal scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci. 2008;49:4898-902 pubmed publisher..bCSLO imaging provides an efficient and noninvasive approach to the longitudinal study of progressive RGC damage. ..
- Müller A, Hauk T, Fischer D. Astrocyte-derived CNTF switches mature RGCs to a regenerative state following inflammatory stimulation. Brain. 2007;130:3308-20 pubmed..These findings could lead to the development of a therapeutic principle for promoting axon regeneration in the CNS as a whole. ..
- Dietz J, Li Y, Chung L, Yandell B, Schlamp C, Nickells R. Rgcs1, a dominant QTL that affects retinal ganglion cell death after optic nerve crush in mice. BMC Neurosci. 2008;9:74 pubmed publisher..A novel dominant locus has been identified that affects sensitivity of ganglion cells to optic nerve crush. The allele responsible for this sensitivity may also be a susceptibility allele for glaucoma. ..
- Moore D, Blackmore M, Hu Y, Kaestner K, Bixby J, Lemmon V, et al. KLF family members regulate intrinsic axon regeneration ability. Science. 2009;326:298-301 pubmed publisher..Thus, coordinated activities of different KLFs regulate the regenerative capacity of CNS neurons. ..
- Payne S, Bartlett C, Harvey A, Dunlop S, Fitzgerald M. Myelin sheath decompaction, axon swelling, and functional loss during chronic secondary degeneration in rat optic nerve. Invest Ophthalmol Vis Sci. 2012;53:6093-101 pubmed publisher..To examine chronic changes occurring at 6 months following partial optic nerve (ON) transection, assessing optic axons, myelin, and visual function...
- Kim S, Kim Y, Park K. Neuroprotective effect of transpupillary thermotherapy in the optic nerve crush model of the rat. Eye (Lond). 2009;23:727-33 pubmed publisher..However, no significant differences in surviving RGCs were demonstrated 2 and 3 mm from the optic nerve head. These results demonstrate that TTT aimed onto the optic nerve head showed a neuroprotective effect. ..
- Parrilla Reverter G, Agudo M, Nadal Nicolás F, Alarcón Martínez L, Jiménez López M, Salinas Navarro M, et al. Time-course of the retinal nerve fibre layer degeneration after complete intra-orbital optic nerve transection or crush: a comparative study. Vision Res. 2009;49:2808-25 pubmed publisher..Importantly, this aberrant pNFH-expression pattern starts earlier and is more dramatic after IONT than after IONC, highlighting the importance that the type of injury has on the time-course of RGC degeneration. ..
- Fischer D, Leibinger M. Promoting optic nerve regeneration. Prog Retin Eye Res. 2012;31:688-701 pubmed publisher..These findings are encouraging and may open the possibility that clinically meaningful regeneration may become achievable one day in the future. ..
- Liu S, Li Z, Weinreb R, Xu G, Lindsey J, Ye C, et al. Tracking retinal microgliosis in models of retinal ganglion cell damage. Invest Ophthalmol Vis Sci. 2012;53:6254-62 pubmed publisher..72, P = 0.004). Longitudinal in vivo imaging of the retinal microglia can provide an effective approach to study microgliosis and its association with RGC degeneration. ..
- Tsai R, Chang C, Sheu M, Huang Z. Anti-apoptotic effects of human granulocyte colony-stimulating factor (G-CSF) on retinal ganglion cells after optic nerve crush are PI3K/AKT-dependent. Exp Eye Res. 2010;90:537-45 pubmed publisher..In conclusion, the anti-apoptotic effects of G-CSF on RGCs are PI3K/AKT signaling dependent in the retinas to rescue RGCs after ON crush injury. ..
- Kirsch M, Trautmann N, Ernst M, Hofmann H. Involvement of gp130-associated cytokine signaling in Müller cell activation following optic nerve lesion. Glia. 2010;58:768-79 pubmed publisher..A potential role of CNTF was possibly masked by a compensatory increase in LIF signaling in the absence of CNTF. ..
- Fischer D, Hauk T, Müller A, Thanos S. Crystallins of the beta/gamma-superfamily mimic the effects of lens injury and promote axon regeneration. Mol Cell Neurosci. 2008;37:471-9 pubmed publisher..These results demonstrate that crystallins of the beta/gamma-superfamily are the lens-derived activators of cascades, which lead to axonal regeneration and suggest that their effects might be mediated by astrocyte-derived CNTF. ..
- Payne S, Bartlett C, Harvey A, Dunlop S, Fitzgerald M. Chronic swelling and abnormal myelination during secondary degeneration after partial injury to a central nervous system tract. J Neurotrauma. 2011;28:1077-88 pubmed publisher..05). Chronic axon swelling and myelin sheath compaction defects are features of secondary degeneration, and may contribute to the reported loss of ON function following partial transection. ..
- Leung C, Weinreb R, Li Z, Liu S, Lindsey J, Choi N, et al. Long-term in vivo imaging and measurement of dendritic shrinkage of retinal ganglion cells. Invest Ophthalmol Vis Sci. 2011;52:1539-47 pubmed publisher..Estimating the probability of RGC survival and measuring the rate of dendritic shrinkage could become a new paradigm for investigating neuronal degeneration and evaluating the response of neuroprotective treatment. ..
- Schweitzer J, Gimnopoulos D, Lieberoth B, Pogoda H, Feldner J, Ebert A, et al. Contactin1a expression is associated with oligodendrocyte differentiation and axonal regeneration in the central nervous system of zebrafish. Mol Cell Neurosci. 2007;35:194-207 pubmed..These complex regulation patterns suggest roles for Cntn1a in myelinating cells and neurons particularly in successful CNS regeneration. ..
- Serbest G, Burkhardt M, Siman R, Raghupathi R, Saatman K. Temporal profiles of cytoskeletal protein loss following traumatic axonal injury in mice. Neurochem Res. 2007;32:2006-14 pubmed..Protection of the axonal cytoskeleton represents a potential therapeutic target for axonal damage associated with injury or neurodegenerative diseases. ..
- Weber A, Harman C. BDNF preserves the dendritic morphology of alpha and beta ganglion cells in the cat retina after optic nerve injury. Invest Ophthalmol Vis Sci. 2008;49:2456-63 pubmed publisher..Thus, development of effective treatment strategies for preserving ganglion cell function in optic nerve-related diseases mandates a clearer understanding of the cellular response characteristics of the specific neurons involved. ..
- Kanamori A, Catrinescu M, Kanamori N, Mears K, Beaubien R, Levin L. Superoxide is an associated signal for apoptosis in axonal injury. Brain. 2010;133:2612-25 pubmed publisher..Early detection of axonal injury with superoxide could serve as a predictive biomarker for patients with optic neuropathy. ..
- Prilloff S, Henrich Noack P, Sabel B. Recovery of axonal transport after partial optic nerve damage is associated with secondary retinal ganglion cell death in vivo. Invest Ophthalmol Vis Sci. 2012;53:1460-6 pubmed publisher..Thus, the accelerated cell death associated with recovery of axon transport suggests the existence of a late retrograde cell death signal. ..
- Zwart I, Hill A, Al Allaf F, Shah M, Girdlestone J, Sanusi A, et al. Umbilical cord blood mesenchymal stromal cells are neuroprotective and promote regeneration in a rat optic tract model. Exp Neurol. 2009;216:439-48 pubmed..Our data indicate that hUCB-derived MSCs may be an easily accessible, widely available source of cells that can contribute towards neural repair through rescue and regeneration of injured neurons. ..
- Fernandes K, Harder J, Kim J, Libby R. JUN regulates early transcriptional responses to axonal injury in retinal ganglion cells. Exp Eye Res. 2013;112:106-17 pubmed publisher..Overall, JUN appears to play a multifaceted role in regulating RGC response to axonal injury. ..
- Ma M, Matthews B, Lampe J, Meaney D, Shofer F, Neumar R. Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury. Exp Neurol. 2009;215:119-27 pubmed publisher..027). There was no differential protection based on axon size. These results support further clinical investigation of temporally optimized therapeutic hypothermia after traumatic brain injury. ..
- Nakatani M, Shinohara Y, Takii M, Mori H, Asai N, Nishimura S, et al. Periocular injection of in situ hydrogels containing Leu-Ile, an inducer for neurotrophic factors, promotes retinal ganglion cell survival after optic nerve injury. Exp Eye Res. 2011;93:873-9 pubmed publisher..These results suggest that periocular delivery of Leu-Ile induces BDNF and GDNF production in the retina, which may eventually enhance RGC survival after ON injury. ..
- Gabriele M, Ishikawa H, Schuman J, Ling Y, Bilonick R, Kim J, et al. Optic nerve crush mice followed longitudinally with spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2011;52:2250-4 pubmed publisher..05 for global and sectoral measurements). SD-OCT can be used to quantitatively monitor changes in retinal thickness in mice over time. ..
- Li Y, Semaan S, Schlamp C, Nickells R. Dominant inheritance of retinal ganglion cell resistance to optic nerve crush in mice. BMC Neurosci. 2007;8:19 pubmed..Inbred mice show different levels of resistance to optic nerve crush. The resistance phenotype is heritable in a dominant fashion involving relatively few loci. Bax was excluded as a candidate gene for this phenotype. ..
- Agudo M, Pérez Marín M, Sobrado Calvo P, Lönngren U, Salinas Navarro M, Cánovas I, et al. Immediate upregulation of proteins belonging to different branches of the apoptotic cascade in the retina after optic nerve transection and optic nerve crush. Invest Ophthalmol Vis Sci. 2009;50:424-31 pubmed publisher
- Hellstrom M, Harvey A. Retinal ganglion cell gene therapy and visual system repair. Curr Gene Ther. 2011;11:116-31 pubmed..We have also combined rAAV gene therapy with pharmacotherapy to determine if cAMP elevation and additional intravitreal injections of growth factors can act synergistically with vector-based delivery of growth-promoting genes. ..
- Liu Y, Gong Z, Liu L, Sun H. Combined effect of olfactory ensheathing cell (OEC) transplantation and glial cell line-derived neurotrophic factor (GDNF) intravitreal injection on optic nerve injury in rats. Mol Vis. 2010;16:2903-10 pubmed..The combination of OEC transplantation and rhGDNF intravitreal injection will be more effective in promoting the recovery of visual function after incomplete injury of the optic nerve in adult rats. ..
- Münzel E, Schaefer K, Obirei B, Kremmer E, Burton E, Kuscha V, et al. Claudin k is specifically expressed in cells that form myelin during development of the nervous system and regeneration of the optic nerve in adult zebrafish. Glia. 2012;60:253-70 pubmed publisher..Our Claudin k antibodies and claudin k:GFP reporter line represent excellent ways to visualize oligodendrocyte and Schwann cell differentiation in vivo. ..
- Fitzgerald M, Bartlett C, Payne S, Hart N, Rodger J, Harvey A, et al. Near infrared light reduces oxidative stress and preserves function in CNS tissue vulnerable to secondary degeneration following partial transection of the optic nerve. J Neurotrauma. 2010;27:2107-19 pubmed publisher..To our knowledge, this is the first demonstration that 670-nm NIR light can reduce oxidative stress and improve function in the CNS following traumatic injury in vivo. ..
- Gupta V, You Y, Klistorner A, Graham S. Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress. Biochim Biophys Acta. 2012;1822:1643-9 pubmed publisher..Collectively, these findings implicate a molecular basis of Shp2 mediated TrkB deactivation leading to RGC degeneration observed in glaucoma. ..
- Fitzgerald M, Bartlett C, Evill L, Rodger J, Harvey A, Dunlop S. Secondary degeneration of the optic nerve following partial transection: the benefits of lomerizine. Exp Neurol. 2009;216:219-30 pubmed publisher..However such an approach may need to be combined with other treatments to ensure long-term maintenance of full visual function. ..
- Gaub P, Joshi Y, Wuttke A, Naumann U, Schnichels S, Heiduschka P, et al. The histone acetyltransferase p300 promotes intrinsic axonal regeneration. Brain. 2011;134:2134-48 pubmed publisher..Therefore, p300 targets both the epigenome and transcription to unlock a post-injury silent gene expression programme that would support axonal regeneration. ..
- Luo J, Cen L, Zhang X, Chiang S, Huang Y, Lin D, et al. PI3K/akt, JAK/STAT and MEK/ERK pathway inhibition protects retinal ganglion cells via different mechanisms after optic nerve injury. Eur J Neurosci. 2007;26:828-42 pubmed..In contrast, the MEK/ERK pathway inhibition protected RGCs via macrophage-independent mechanism(s). ..
- Sullivan T, Geisert E, Templeton J, Rex T. Dose-dependent treatment of optic nerve crush by exogenous systemic mutant erythropoietin. Exp Eye Res. 2012;96:36-41 pubmed publisher..Furthermore, EPO-R76E induced a dose-dependent rise in the hematocrit that was still attenuated as compared to wild-type EPO. ..
- Knöferle J, Koch J, Ostendorf T, Michel U, Planchamp V, Vutova P, et al. Mechanisms of acute axonal degeneration in the optic nerve in vivo. Proc Natl Acad Sci U S A. 2010;107:6064-9 pubmed publisher..Both processes are proposed to be major targets for the manipulation of axonal degeneration in future therapeutic settings. ..
- Wang R, Xie J, Kang Z, Sun X, Chen N, Liu L, et al. Hyperbaric oxygen preconditioning promotes survival of retinal ganglion cells in a rat model of optic nerve crush. J Neurotrauma. 2010;27:763-70 pubmed publisher..These results demonstrate that HBO-PC appears to be neuroprotective against ONC insult via inhibition of neuronal apoptosis pathways. ..
- Zhao T, Li Y, Tang L, Li Y, Fan F, Jiang B. Protective effects of human umbilical cord blood stem cell intravitreal transplantation against optic nerve injury in rats. Graefes Arch Clin Exp Ophthalmol. 2011;249:1021-8 pubmed publisher..The protective mechanism is correlated with the continuous secretion of BDNF and GDNF in vivo of retina in optic nerve injury rats by the transplanted hUCBSCs. ..
- Guo Y, Johnson E, Cepurna W, Dyck J, Doser T, Morrison J. Early gene expression changes in the retinal ganglion cell layer of a rat glaucoma model. Invest Ophthalmol Vis Sci. 2011;52:1460-73 pubmed publisher..Most likely, these changes represent those specific to RGCs and are thus potentially important for enhancing RGC survival in glaucoma. ..
- Harvey A, Hellstrom M, Rodger J. Gene therapy and transplantation in the retinofugal pathway. Prog Brain Res. 2009;175:151-61 pubmed publisher..Analysis of regenerating RGCs intracellularly injected with lucifer yellow indicates gene-specific changes in dendritic structure that likely impact upon visual function. ..