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Med.Weter. 9 exploration of the physiological mechanism.It also 4.Brunori M..Vallone B.:Neuroglobin,seven years later.Cell Mol.Life Sci. enhances cell viability under hypoxia and under vari- 2007,64,1259-1268,doi:10.1007/s00018-007-7090-2 5.Burmester T.Weich B.,Reinhardt S..Hankeln T.:A vertebrate globin expressed ous types of oxidative stress in transgenic systems,but in the brain.Nature 2000,407,6803,520-523 does not appear to be strongly upregulated in response 6.Burmester T..Haberkamp M..Mit S..Roesner A..Schmidt M.Ebner B.. to stress(7).Additionally,Xu et al.(24)reported that Gerlach F.Fuchs C..Hankeln T.:Neuroglobin and Cytoglobin:Genes, Proteins and Evolution.IUBMB Life.2004,56,703-707,doi:10.1080/ the Ngb distribution in the presynaptic structure of 15216540500037257. rat retina between synaptic vesicles have more levels 7.Burmester T..Hankeln T:What Is the Function of Neuroglobin?J.Exp.Biol. of Ngb expression in males than females and further 2009,212,1423-1428,doi:10.1242/jeb.000729. supports the Ngb protein which is assumed to be as- 8.Chan S.,Saraswathy S..Rehak M.,Rao N.:Neuroglobin protection in retinal ischemia.Invest.Ophthalmol.Vis.Sci.2012,532,704-711. sociated with the retinal oxygen consumption.This 9.Costa B..Fawcett R,Li G.Y.,Safa N.N.:Orally administered epigallocatechin has suggested that Ngb protein can be secreted by the gallate attenuates slight induced photoreceptor damage.Brain research bulletin neurons and transported between synaptic vesicles to 2008.764,412-423 10.Ding G..Yan Z,He T.:The appearance of white and red eggs in rat retina dur- complete complex physiological functions.The expres- ing the death of acute ischemic ganglion cells.Zhonghua eye science journal sion of Ngb in different retinal layers may correspond 2010,467,590-596. to the sensitivity ofeach layer to ischemic and hypoxic 11.Ding G.:Research status of brain-globin in the retina.Journal of clinical injury.Ding et al.(11)found that in the acute ischemic ophthalmology 2010,186,573-575. 12.Fordel E.,Thijs L,Martinet W..Schrijvers D..Moens L.Dewilde S.:Anoxiaor and hypoxic state,the increase of Ngb in the cerebral of oxygen and glucose deprivation in sh-sy5y cells:astep closer to the unraveling the rat's retina was mainly concentrated in the nodule of neuroglobin and cytoglobin functions.Gene 2007,3982,114-122. 13.Geuens E.,Brouns 1..Flamez D.,Dewilde S.,Timmermans J..Moens L.: cell layer,and less expression observed in the inner A globin in the nucleus.J.Biol.Chem.2003,278,30417-30420 and outer reticular layer.The experimental results of 14.Greenberg D.,Jin K.,Khan A.:Neuroglobin:an endogenous neuroprotectant. the current study also reported that Ngb showed high Current opinion in pharmacology 2008,81,20-24. intensity in the optic nerve fiber layer,network layer, 15.Li Y..Liu H..Tong Y.:Immunohistochemistry of the distribution of brain globin in rat eyeball.Ophthalmic Research 2000,245,46 1-4 4. outer plexiform layer,and the light receptors.In areas 16.Nayak G.,Prentice M..Milton S.:Role of neuroglobin in regulating reactive such as the ganglion cells and kernel layer,the strength oxygen species in the brain of the anoxia-tolerant turtle trachemys scripta. of Ngb expression is weak.Other layers including Journal of neurochemistry 2010,1102,603-612. 17.Ostojic J..Gro-danic D.S..Syed N.A.,Hargrove M.S.,Trent J.T..Kuehn the optic nerve fiber layer,inner and outer plexiform M.H.,Kwon Y.H.,Kardon R.H.,Sakaguchi S.D.:Patterns of distribution layer,and optical sensors consumed the highest level of oxygen-binding globins,neuroglobin and cytoglobin in the human retina. of oxygen and they are the most concentrated areas of Arch.Ophthalmol.2008,12611,1530-1536. 18.Ostoji J.,Sakaguchi D.,De Lathouder Y..Hargrove M.S..Trent J.T.,Kwon high ischemia hypoxia sensitivity.In addition,the thin Y.H..Kardon R.H..Kuehn M.H.,Betts D.M..Grozdanic S.:Neuroglobin cell layer channels information to the brain while the and cytoglobin:oxygen-binding proteins in retinal neurons.Investigative retina kernel layer as impulse transfer photoreceptor ophthalmology visual science.2006,473,1016-1023 cells to access the ganglion cells.Both have a high 19.Ran J..Sun .Bi Expression of Neuroglobin mRNA in rat eyeball. Chongqing med..2003,47,1035-1036. demand for oxygen,and are highly sensitive to isch- 20.Roberts A.,Gaffney E..Luthert P.J.,Foss A.,Bryne H.:Retinal oxygen dis- emia hypoxia.The outer nuclear layer,photoreceptor tribution and the role of Neuroglobin.Joumal of mathematical biology 2016, outer segments,and pigment on the cortex of the brain 731,1-38. 21.Schmidt M.,Giessl A.,Laufs T.,Hankeln T,Wolfrum U.,Burmester T.:How showed Negative Ngb expression and express least does the eye breath?Evidence for neuroglobin-mediated oxygen supply in sensitive to the demand for oxygen. the mammalian retina.J.Biol.Chem.2783,1932-1935. The reported results have suggested that Ngb may 22.Shi S..Feng X.:Expression of myoglobin in acute retinal ischemic injury in rats.Ophthalmic Research 2009,2710,915-918. have an important physiological role in maintaining 23.Wei..Deng Y..Li:How can photoreceptor cells breathe in the retina? retinal oxygen homeostasis and participating in the Neuroglobin may be the answer.Neural regeneration research 2010,59, repair mechanism of light damage in extreme survival 720-720. to adapt to environmental conditions.The study further 24.Xu O.,Huang X..Wei X.:Ultrastructural study of the intraretinal distribution of neuroglobin proteins in normal adult rats.International journal of ophthal- provides a theoretical basis for in-depth research of the mology.91.35-37.(In Chinese). Ngb physiological function in the retina and recorded 25.Xu O..Huang F,Wei Y.:Subcellular distribution of myoglobin expression in morphological data for further exploring the distribu- the retina of adult rats.International joural ofophthalmology.2009,1,35-37 (in Chinese with English abstract) tion of Ngb in normal mammalian retinas.However, 26.Yu Y.,CringleJ.:Oxygen distribution and consumption within the retina in the mechanism of Ngb involvement in damage repair vascularized and avascular retinas and animal models of retinal disease.Prog. after retinal injury remains to be studied further in Retina Eye Res.2001,202,175-208. 27.Yan G.,Yue H.,Duan W.:The effect of oxygen on the surface of membrane- molecular and tissue biology. encephaloglobin in rabbit optic network.New progress in ophthalmology 2010,307,618-621. References 28.Yang y.Liu Gao Distribution of Neuroglobin in the retina of adult sheep.Chinese Journal of anatomy 2015,3,275-278(In Chinese). 1.Alekseeva O.S..Grigorev J.P.,Korzhewskij D.E.:Neuroglobin,an oxygen- 29.Ying Q..Feng Y.Z.Guang H.P..YuZ.Guang M.W.Wen Z.W.Jing M.Shi binding protein in the mammalian nervous system(localization and putative R.:Characteristics and visual outcomes of patients hospitalized for ocular functions).J.Evolut.Biochem.Physiolog.2017,53,249-258. trauma in central China.Interational Journal of Ophthalmology 2015,8, 2.Anderson B.:Ocular effects of changes in oxygen and carbon dioxide tension. 162-168. Trans Am.Ophthalmol.Soc.1968,66,423-474. 3.Bentmann A.,Schmidt M.,Reuss S..Wolfrum U..Hankeln T..Brumester T.: Corresponding Author:Xia Liu,College of Life Science and Technology, Divergent distribution in vascular and avascular mammalian retinae links Gansu Agricultural University,Lanzhou City,Gansu Province,People's neuroglobin into cellular respiration.J.Biochem.2005,280,21,20660-20665. Republic of ChinaMed. Weter. 9 exploration of the physiological mechanism. It also enhances cell viability under hypoxia and under vari￾ous types of oxidative stress in transgenic systems, but does not appear to be strongly upregulated in response to stress (7). Additionally, Xu et al. (24) reported that the Ngb distribution in the presynaptic structure of rat retina between synaptic vesicles have more levels of Ngb expression in males than females and further supports the Ngb protein which is assumed to be as￾sociated with the retinal oxygen consumption. This has suggested that Ngb protein can be secreted by the neurons and transported between synaptic vesicles to complete complex physiological functions. The expres￾sion of Ngb in different retinal layers may correspond to the sensitivity of each layer to ischemic and hypoxic injury. Ding et al. (11) found that in the acute ischemic and hypoxic state, the increase of Ngb in the cerebral of the rat’s retina was mainly concentrated in the nodule cell layer, and less expression observed in the inner and outer reticular layer. The experimental results of the current study also reported that Ngb showed high intensity in the optic nerve fiber layer, network layer, outer plexiform layer, and the light receptors. In areas such as the ganglion cells and kernel layer, the strength of Ngb expression is weak. Other layers including the optic nerve fiber layer, inner and outer plexiform layer, and optical sensors consumed the highest level of oxygen and they are the most concentrated areas of high ischemia hypoxia sensitivity. In addition, the thin cell layer channels information to the brain while the retina kernel layer as impulse transfer photoreceptor cells to access the ganglion cells. Both have a high demand for oxygen, and are highly sensitive to isch￾emia hypoxia. The outer nuclear layer, photoreceptor outer segments, and pigment on the cortex of the brain showed Negative Ngb expression and express least sensitive to the demand for oxygen. The reported results have suggested that Ngb may have an important physiological role in maintaining retinal oxygen homeostasis and participating in the repair mechanism of light damage in extreme survival to adapt to environmental conditions. The study further provides a theoretical basis for in-depth research of the Ngb physiological function in the retina and recorded morphological data for further exploring the distribu￾tion of Ngb in normal mammalian retinas. However, the mechanism of Ngb involvement in damage repair after retinal injury remains to be studied further in molecular and tissue biology. References 1. Alekseeva O. S., Grigorev J. P., Korzhewskij D. E.: Neuroglobin, an oxygen￾binding protein in the mammalian nervous system (localization and putative functions). J. Evolut. Biochem. Physiolog. 2017, 53, 249-258. 2. Anderson B.: Ocular effects of changes in oxygen and carbon dioxide tension. Trans Am. Ophthalmol. Soc. 1968, 66, 423-474. 3. Bentmann A., Schmidt M., Reuss S., Wolfrum U., Hankeln T., Brumester T.: Divergent distribution in vascular and avascular mammalian retinae links neuroglobin into cellular respiration. J. Biochem. 2005, 280, 21, 20660-20665. 4. Brunori M., Vallone B.: Neuroglobin, seven years later. Cell Mol. Life Sci. 2007, 64, 1259-1268, doi: 10.1007/s00018-007-7090-2. 5. Burmester T., Weich B., Reinhardt S., Hankeln T.: A vertebrate globin expressed in the brain. Nature 2000, 407, 6803, 520-523. 6. Burmester T., Haberkamp M., Mitz S., Roesner A., Schmidt M., Ebner B., Gerlach F., Fuchs C., Hankeln T.: Neuroglobin and Cytoglobin: Genes, Proteins and Evolution. IUBMB Life. 2004, 56, 703-707, doi: 10.1080/ 15216540500037257. 7. Burmester T., Hankeln T.: What Is the Function of Neuroglobin? J. Exp. Biol. 2009, 212, 1423-1428, doi: 10.1242/jeb.000729. 8. Chan S., Saraswathy S., Rehak M., Rao N.: Neuroglobin protection in retinal ischemia. Invest. Ophthalmol. Vis. Sci. 2012, 532, 704-711. 9. Costa B., Fawcett R., Li G. Y., Safa N. N.: Orally administered epigallocatechin gallate attenuates slight induced photoreceptor damage. Brain research bulletin 2008, 764, 412-423. 10. Ding G., Yan Z., He T.: The appearance of white and red eggs in rat retina dur￾ing the death of acute ischemic ganglion cells. Zhonghua eye science journal 2010, 467, 590-596. 11. Ding G.: Research status of brain-globin in the retina. Journal of clinical ophthalmology 2010, 186, 573-575. 12. Fordel E., Thijs L., Martinet W., Schrijvers D., Moens L., Dewilde S.: Anoxia or oxygen and glucose deprivation in sh-sy5y cells: a step closer to the unraveling of neuroglobin and cytoglobin functions. Gene 2007, 3982, 114-122. 13. Geuens E., Brouns I., Flamez D., Dewilde S., Timmermans J., Moens L.: A globin in the nucleus. J. Biol. Chem. 2003, 278, 30417-30420. 14. Greenberg D., Jin K., Khan A.: Neuroglobin: an endogenous neuroprotectant. Current opinion in pharmacology 2008, 81, 20-24. 15. Li Y., Liu H., Tong Y.: Immunohistochemistry of the distribution of brain globin in rat eyeball. Ophthalmic Research 2000, 245, 46 1-4 4. 16. Nayak G., Prentice M., Milton S.: Role of neuroglobin in regulating reactive oxygen species in the brain of the anoxia-tolerant turtle trachemys scripta. Journal of neurochemistry 2010, 1102, 603-612. 17. Ostojic J., Grozdanic D. S., Syed N. A., Hargrove M. S., Trent J. T., Kuehn M. H., Kwon Y. H., Kardon R. H., Sakaguchi S. D.: Patterns of distribution of oxygen-binding globins, neuroglobin and cytoglobin in the human retina. Arch. Ophthalmol. 2008, 12611, 1530-1536. 18. Ostoji J., Sakaguchi D., De Lathouder Y., Hargrove M. S., Trent J. T., Kwon Y. H., Kardon R. H., Kuehn M. H., Betts D. M., Grozdanic S.: Neuroglobin and cytoglobin: oxygen-binding proteins in retinal neurons. Investigative ophthalmology & visual science. 2006, 473,1016-1023. 19. Ran J., Sun Q., Bi X.: Expression of Neuroglobin mRNA in rat eyeball. Chongqing med. 2003, 47, 1035-1036. 20. Roberts A., Gaffney E., Luthert P. J., Foss A., Bryne H.: Retinal oxygen dis￾tribution and the role of Neuroglobin. Journal of mathematical biology 2016, 731, 1-38. 21. Schmidt M., Giessl A., Laufs T., Hankeln T., Wolfrum U., Burmester T.: How does the eye breath? Evidence for neuroglobin-mediated oxygen supply in the mammalian retina. J. Biol. Chem. 2783, 1932-1935. 22. Shi S., Feng X.: Expression of myoglobin in acute retinal ischemic injury in rats. Ophthalmic Research 2009, 2710, 915-918. 23. Wei X., Deng Y., Liu X.: How can photoreceptor cells breathe in the retina? Neuroglobin may be the answer. Neural regeneration research 2010, 59, 720-720. 24. Xu Q., Huang X., Wei X.: Ultrastructural study of the intraretinal distribution of neuroglobin proteins in normal adult rats. International journal of ophthal￾mology. 91, 35-37. (In Chinese). 25. Xu Q., Huang F., Wei Y.: Subcellular distribution of myoglobin expression in the retina of adult rats. International journal of ophthalmology. 2009, 1, 35-37 (in Chinese with English abstract). 26. Yu Y., Cringle J.: Oxygen distribution and consumption within the retina in vascularized and avascular retinas and animal models of retinal disease. Prog. Retina Eye Res. 2001, 202, 175-208. 27. Yan G., Yue H., Duan W.: The effect of oxygen on the surface of membrane￾encephaloglobin in rabbit optic network. New progress in ophthalmology 2010, 307, 618-621. 28. Yang Y., Liu X., Gao X.: Distribution of Neuroglobin in the retina of adult sheep. Chinese Journal of anatomy 2015, 3, 275-278 (In Chinese). 29. Ying Q., Feng Y. Z., Guang H. P., Yu Z., Guang M. W., Wen Z. W., Jing M., Shi J. R.: Characteristics and visual outcomes of patients hospitalized for ocular trauma in central China. International Journal of Ophthalmology 2015, 8, 162-168. Corresponding Author: Xia Liu, College of Life Science and Technology, Gansu Agricultural University, Lanzhou City, Gansu Province, People’s Republic of China
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