Effect of light on global gene expression in the neuroglobin-deficient mouse retina

Ilmjärv,Sten; Reimets,Riin; Hundahl,Christian  Ansgar; Luuk,Hendrik

doi:10.3892/br.2014.364

Effect of light on global gene expression in the neuroglobin-deficient mouse retina

Authors:
- Sten Ilmjärv
- Riin Reimets
- Christian Ansgar Hundahl
- Hendrik Luuk
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Affiliations: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia
Published online on: September 15, 2014 https://doi.org/10.3892/br.2014.364
Pages: 780-786

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Abstract

Several previous studies have raised controversy over the functional role of neuroglobin (Ngb) in the retina. Certain studies indicate a significant impact of Ngb on retinal physiology, whereas others are conflicting. The present is an observational study that tested the effect of Ngb deficiency on gene expression in dark‑ and light‑adapted mouse retinas. Large‑scale gene expression profiling was performed using GeneChip® Mouse Exon 1.0 ST arrays and the results were compared to publicly available data sets. The lack of Ngb was found to have a minor effect on the light‑induced retinal gene expression response. In addition, there was no increase in the expression of marker genes associated with hypoxia, endoplasmic reticulum‑stress and oxidative stress in the Ngb‑deficient retina. By contrast, several genes were identified that appeared to be differentially expressed between the genotypes when the effect of light was ignored. The present study indicates that Ngb deficiency does not lead to major alternations in light‑dependent gene expression response, but leads to subtle systemic differences of a currently unknown functional significance.

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1	Anderson B Jr and Saltzman HA: Retinal oxygen utilization measured by hyperbaric blackout. Arch Ophthalmol. 72:792–795. 1964. View Article : Google Scholar : PubMed/NCBI
2	Ames A III: Energy requirements of CNS cells as related to their function and to their vulnerability to ischemia: a commentary based on studies on retina. Can J Physiol Pharmacol. 70(Suppl): S158–S164. 1992. View Article : Google Scholar : PubMed/NCBI
3	Ahmed J, Braun RD, Dunn R Jr and Linsenmeier RA: Oxygen distribution in the macaque retina. Invest Ophthalmol Vis Sci. 34:516–521. 1993.
4	Linsenmeier RA: Effects of light and darkness on oxygen distribution and consumption in the cat retina. J Gen Physiol. 88:521–542. 1986. View Article : Google Scholar : PubMed/NCBI
5	Burmester T, Weich B, Reinhardt S and Hankeln T: A vertebrate globin expressed in the brain. Nature. 407:520–523. 2000. View Article : Google Scholar : PubMed/NCBI
6	Dewilde S, Kiger L, Burmester T, et al: Biochemical characterization and ligand binding properties of neuroglobin, a novel member of the globin family. J Biol Chem. 276:38949–38955. 2001. View Article : Google Scholar : PubMed/NCBI
7	Schmidt M, Giessl A, Laufs T, Hankeln T, Wolfrum U and Burmester T: How does the eye breathe? Evidence for neuroglobin-mediated oxygen supply in the mammalian retina. J Biol Chem. 278:1932–1935. 2003. View Article : Google Scholar : PubMed/NCBI
8	Bentmann A, Schmidt M, Reuss S, Wolfrum U, Hankeln T and Burmester T: Divergent distribution in vascular and avascular mammalian retinae links neuroglobin to cellular respiration. J Biol Chem. 280:20660–20665. 2005. View Article : Google Scholar : PubMed/NCBI
9	Wei X, Yu Z, Cho KS, et al: Neuroglobin is an endogenous neuroprotectant for retinal ganglion cells against glaucomatous damage. Am J Pathol. 179:2788–2797. 2011. View Article : Google Scholar : PubMed/NCBI
10	Shi SY, Feng XM, Li Y, Li X and Chen XL: Expression of neuroglobin in ocular hypertension induced acute hypoxic-ischemic retinal injury in rats. Int J Ophthalmol. 4:393–395. 2011.PubMed/NCBI
11	Lechauve C, Rezaei H, Celier C, et al: Neuroglobin and prion cellular localization: investigation of a potential interaction. J Mol Biol. 388:968–977. 2009. View Article : Google Scholar : PubMed/NCBI
12	Rajendram R and Rao NA: Neuroglobin in normal retina and retina from eyes with advanced glaucoma. Br J Ophthalmol. 91:663–666. 2007. View Article : Google Scholar : PubMed/NCBI
13	Chan AS, Saraswathy S, Rehak M, Ueki M and Rao NA: Neuroglobin protection in retinal ischemia. Invest Ophthalmol Vis Sci. 53:704–711. 2012. View Article : Google Scholar : PubMed/NCBI
14	Lechauve C, Augustin S, Cwerman-Thibault H, et al: Neuroglobin involvement in respiratory chain function and retinal ganglion cell integrity. Biochim Biophys Acta. 1823.2261–2273. 2012.PubMed/NCBI
15	Hundahl CA, Fahrenkrug J, Luuk H, Hay-Schmidt A and Hannibal J: Restricted expression of neuroglobin in the mouse retina and co-localization with melanopsin and tyrosine hydroxylase. Biochem Biophys Res Commun. 425:100–106. 2012. View Article : Google Scholar : PubMed/NCBI
16	Raida Z, Hundahl CA, Kelsen J, Nyengaard JR and Hay-Schmidt A: Reduced infarct size in neuroglobin-null mice after experimental stroke in vivo. Exp Transl Stroke Med. 4:152012. View Article : Google Scholar : PubMed/NCBI
17	Hundahl CA, Luuk H, Ilmjarv S, et al: Neuroglobin-deficiency exacerbates Hif1A and c-FOS response, but does not affect neuronal survival during severe hypoxia in vivo. PLoS One. 6:e281602011. View Article : Google Scholar : PubMed/NCBI
18	Hundahl CA, Fahrenkrug J, Hay-Schmidt A, Georg B, Faltoft B and Hannibal J: Circadian behaviour in neuroglobin deficient mice. PLoS One. 7:e344622012. View Article : Google Scholar : PubMed/NCBI
19	Ilmjarv S, Hundahl CA, Reimets R, et al: Estimating differential expression from multiple indicators. Nucleic Acids Res. 42:e722014. View Article : Google Scholar : PubMed/NCBI
20	Bedolla DE and Torre V: A component of retinal light adaptation mediated by the thyroid hormone cascade. PLoS One. 6:e263342011. View Article : Google Scholar : PubMed/NCBI
21	Porterfield VM, Piontkivska H and Mintz EM: Identification of novel light-induced genes in the suprachiasmatic nucleus. BMC Neurosci. 8:982007. View Article : Google Scholar : PubMed/NCBI
22	Reimand J, Arak T and Vilo J: g:Profiler - a web server for functional interpretation of gene lists (2011 update). Nucleic Acids Res. 39:W307–W315. 2011. View Article : Google Scholar : PubMed/NCBI
23	Benjamini Y and Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc Ser B. 57:289–300. 1995.
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
25	Araki R, Nakahara M, Fukumura R, et al: Identification of genes that express in response to light exposure and express rhythmically in a circadian manner in the mouse suprachiasmatic nucleus. Brain Res. 1098:9–18. 2006. View Article : Google Scholar : PubMed/NCBI
26	Hota KB, Hota SK, Srivastava RB and Singh SB: Neuroglobin regulates hypoxic response of neuronal cells through Hif-1α- and Nrf2-mediated mechanism. J Cereb Blood Flow Metab. 32:1046–1060. 2012.PubMed/NCBI
27	Mendez O, Zavadil J, Esencay M, et al: Knock down of HIF-1alpha in glioma cells reduces migration in vitro and invasion in vivo and impairs their ability to form tumor spheres. Mol Cancer. 9:1332010. View Article : Google Scholar : PubMed/NCBI
28	Linker RA, Lee DH, Ryan S, et al: Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 134:678–692. 2011. View Article : Google Scholar : PubMed/NCBI
29	Iwakoshi NN, Lee AH, Vallabhajosyula P, Otipoby KL, Rajewsky K and Glimcher LH: Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat Immunol. 4:321–329. 2003. View Article : Google Scholar : PubMed/NCBI
30	Ostojic J, Grozdanic SD, Syed NA, et al: Patterns of distribution of oxygen-binding globins, neuroglobin and cytoglobin in human retina. Arch Ophthalmol. 126:1530–1536. 2008. View Article : Google Scholar : PubMed/NCBI
31	Ostojic J, Sakaguchi DS, de Lathouder Y, et al: Neuroglobin and cytoglobin: oxygen-binding proteins in retinal neurons. Invest Ophthalmol Vis Sci. 47:1016–1023. 2006. View Article : Google Scholar : PubMed/NCBI
32	Schmidt M, Laufs T, Reuss S, Hankeln T and Burmester T: Divergent distribution of cytoglobin and neuroglobin in the murine eye. Neurosci Lett. 374:207–211. 2005. View Article : Google Scholar : PubMed/NCBI
33	Fago A, Hundahl C, Malte H and Weber RE: Functional properties of neuroglobin and cytoglobin. Insights into the ancestral physiological roles of globins. IUBMB Life. 56:689–696. 2004. View Article : Google Scholar : PubMed/NCBI
34	Schalkwyk LC, Fernandes C, Nash MW, Kurrikoff K, Vasar E and Koks S: Interpretation of knockout experiments: the congenic footprint. Genes Brain Behav. 6:299–303. 2007. View Article : Google Scholar : PubMed/NCBI
35	Biederbick A, Rose S and Elsasser HP: A human intracellular apyrase-like protein, LALP70, localizes to lysosomal/autophagic vacuoles. J Cell Sci. 112:2473–2484. 1999.PubMed/NCBI
36	Cacciagli P, Haddad MR, Mignon-Ravix C, et al: Disruption of the ATP8A2 gene in a patient with a t(10;13) de novo balanced translocation and a severe neurological phenotype. Eur J Hum Genet. 18:1360–1363. 2010. View Article : Google Scholar : PubMed/NCBI
37	Coleman JA, Kwok MC and Molday RS: Localization, purification, and functional reconstitution of the P4-ATPase Atp8a2, a phosphatidylserine flippase in photoreceptor disc membranes. J Biol Chem. 284:32670–32679. 2009. View Article : Google Scholar : PubMed/NCBI
38	Zhu X, Libby RT, de Vries WN, et al: Mutations in a P-type ATPase gene cause axonal degeneration. PLoS Genet. 8:e10028532012. View Article : Google Scholar : PubMed/NCBI
39	Coleman JA, Zhu X, Djajadi HR, et al: Phospholipid flippase ATP8A2 is required for normal visual and auditory function and photoreceptor and spiral ganglion cell survival. J Cell Sci. 127:1138–1149. 2014. View Article : Google Scholar : PubMed/NCBI
40	Franceschini A, Szklarczyk D, Frankild S, et al: STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 41:D808–D815. 2013. View Article : Google Scholar : PubMed/NCBI