The effect of form deprivation on the morphology of retinal ganglion cells in mice_Chinese Journal of Ocular Fundus Diseases

Authors：

Zhi Zhina , Sun Cuimin , Fu Qian , Chen Si ,  Zhou Xiangtian

School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health P.R.China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou 325003, China;

Corresponding author：

Zhou Xiangtian, Email: zxt-dr@wz.zj.cn

Keywords：

Myopia, degenerative; Vision, ocular; Retinal ganglion cells; Dendrites; Animal experimentation

DOI：

10.3760/cma.j.issn.1005-1015.2019.05.006

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effects of form deprivation on the morphology of different types of RGC in mice.Methods Sixty B6.Cg-Tg (Thy1-YFP) HJrs/J transgenic mice were randomly assigned to form-deprived group (n=28) and control group (n=32). The right eyes of mice in the form-deprived group were covered by an occluder for 2 weeks as experimental eyes. The right eyes of mice in the control group were taken as control eyes. Before and 2 weeks after form deprivation, the refraction and ocular biometrics were measured; RGC were stained with Bra3a antibody and counted; the morphology of RGC was reconstructed with Neuroexplore software after immunohistochemical staining. The data was compared among experimental eyes, fellow eyes and control eyes by one-way analysis of variance.Results Two weeks after form deprivation, the axial myopia was observed in the experimental eyes (refraction: F=15.009, P＜0.001; vitreous chamber depth: F=3.360, P=0047; ocluar axial length: F=5.011, P=0013). The number of RGC in central retina of the experimental eyes was decreased compared with the fellow eyes and the control eyes (F=4.769, P=0.035). The reconstructed RGC were classified into 4 types according to their dendritic morphology. Form deprivation affected all 4 types of RGC but in a different way. Among them, 3 types of RGC were likely contribute to form vision perception. Form deprivation increased the dendrite branches in these types of ganglion cells. However, form deprivation decreasd dendrite segment numbers in both eyes and the intersection and length insholl analyse type 4 ganglion cells which were morphologically identified as ipRGC.Conclusion Form deprivation distinguishingly affects the morphology of different types of RGC, indicating that form vision and non-form vision play different role in myopia development.

Citation： Zhi Zhina, Sun Cuimin, Fu Qian, Chen Si, Zhou Xiangtian. The effect of form deprivation on the morphology of retinal ganglion cells in mice. Chinese Journal of Ocular Fundus Diseases, 2019, 35(5): 451-461. doi: 10.3760/cma.j.issn.1005-1015.2019.05.006 Copy

1.	Zhi Z, Pan M, Xie R, et al. The effect of temporal and spatial stimuli on the refractive status of guinea pigs following natural emmetropization[J]. Invest Ophthalmol Vis Sci, 2013, 54(1): 890-897. DOI: 10.1167/iovs.11-8064.
2.	Ashby RS, Schaeffel F. The effect of bright light on lens compensation in chicks[J]. Invest Ophthalmol Vis Sci, 2010, 51(10): 5247-5253. DOI: 10.1167/iovs.09-4689.
3.	Park SJ, Kim IJ, Looger LL, et al. Excitatory synaptic inputs to mouse on-off direction-selective retinal ganglion cells lack direction tuning[J]. J Neurosci, 2014, 34(11): 3976-3981. DOI: 10.1523/JNEUROSCI.5017-13.2014.
4.	Freed MA. Asymmetry between ON and OFF alpha ganglion cells of mouse retina: integration of signal and noise from synaptic inputs[J]. J Physiol, 2017, 595(22): 6979-6991. DOI: 10.1113/JP274736.
5.	Pickard GE, Sollars PJ. Intrinsically photosensitive retinal ganglion cells[J]. Rev Physiol Biochem Pharmacol, 2012, 162: 59-90. DOI: 10.1007/112_2011_4.
6.	Pan F. Defocused image changes signaling of ganglion cells in the mouse retina[J/OL]. Cells, 2019, 8(7): 640[2019-06-26].http://www.mdpi.com/resolver?pii=cells8070640. DOI: 10.3390/cells8070640.
7.	Mwachaka PM, Saidi H, Odula PO, et al. Effect of monocular deprivation on rabbit neural retinal cell densities[J]. J Ophthalmic Vis Res, 2015, 10(2): 144-150. DOI: 10.4103/2008-322X.163770.
8.	Chakraborty R, Park HN, Hanif AM, et al. ON pathway mutations increase susceptibility to form-deprivation myopia[J]. Exp Eye Res, 2015, 137: 79-83. DOI: 10.1016/j.exer.2015.06.009.
9.	Liu W, Khare SL, Liang X, et al. All Brn3 genes can promote retinal ganglion cell differentiation in the chick[J]. Development, 2000, 127(15): 3237-3247.
10.	Turner EE, Jenne KJ, Rosenfeld MG. Brn-3.2: a Brn-3-related transcription factor with distinctive central nervous system expression and regulation by retinoic acid[J]. Neuron, 1994, 12(1): 205-218. DOI: 10.1016/0896-6273(94)90164-3.
11.	Sengpiel F, Kind PC. The role of activity in development of the visual system[J]. Curr Biol, 2002, 12(23): 818-826. DOI: 10.1016/s0960-9822(02)01318-0.
12.	Mui AM, Yang V, Aung MH, et al. Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina[J/OL]. PLoS One, 2018, 13(2): 0192435[2018-02-06].https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192435. DOI: 10.1371/journal.pone.0192435.
13.	Cellerino AKohler K. Brain-derived neurotrophic factor/neurotrophin-4 receptor TrkB is localized on ganglion cells and dopaminergic amacrine cells in the vertebrate retina[J]. J Comp Neurol, 1997, 386(1): 149-160. DOI: 10.1002/(SICI)1096-9861(19970915)386:1<149::AID-CNE13>3.0.CO;2-F.
14.	Chitranshi N, Dheer Y, Mirzaei M, et al. Loss of Shp2 rescues BDNF/TrkB signaling and contributes to improved retinal ganglion cell neuroprotection[J]. Mol Ther, 2019, 27(2): 424-441. DOI: 10.1016/j.ymthe.2018.09.019.
15.	Xu L, Zhang Z, Xie T, et al. Inhibition of BDNF-AS provides neuroprotection for retinal ganglion cells against ischemic injury[J/OL]. PLoS One, 2016, 11(12): 0164941[2016-012-09]. http://dx.plos.org/10.1371/journal.pone.0164941. DOI: 10.1371/journal.pone.0164941.
16.	Sanchez-Migallon MC, Valiente-Soriano FJ, Nadal-Nicolas FM, et al. Apoptotic retinal ganglion cell death after optic nerve transection or crush in mice: delayed RGC loss with BDNF or a caspase 3 inhibitor[J]. Invest Ophthalmol Vis Sci, 2016, 57(1): 81-93. DOI: 10.1167/iovs.15-17841.
17.	Oshitari T, Yoshida-Hata N, Yamamoto S. Effect of neurotrophic factors on neuronal apoptosis and neurite regeneration in cultured rat retinas exposed to high glucose[J]. Brain Res, 2010, 1346: 43-51. DOI: 10.1016/j.brainres.2010.05.073.
18.	Liang Y, Yu YH, Yu HJ, et al. Effect of BDNF-TrKB pathway on apoptosis of retinal ganglion cells in glaucomatous animal model[J]. Eur Rev Med Pharmacol Sci, 2019, 23(9): 3561-3568. DOI: 10.26355/eurrev_201905_17777.
19.	Varella MH, de Mello FG, Linden R. Evidence for an antiapoptotic role of dopamine in developing retinal tissue[J]. J Neurochem, 1999, 73(2): 485-492. DOI: 10.1046/j.1471-4159.1999.0730485.x.
20.	Dong J, Gao L, Han J, et al. Dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina independent of early synchronized spontaneous network activity[J]. Mol Neurobiol, 2017, 54(5): 3407-3417. DOI: 10.1007/s12035-016-9914-2.
21.	Lin B, Wang SW. Masland RH retinal ganglion cell type, size, and spacing can be specified independent of homotypic dendritic contacts[J]. Neuron, 2004, 43(4): 475-485. DOI: 10.1016/j.neuron.2004.08.002.
22.	Geeraerts E, Dekeyster E, Gaublomme D, et al. A freely available semi-automated method for quantifying retinal ganglion cells in entire retinal flatmounts[J]. Exp Eye Res, 2016, 147: 105-113. DOI: 10.1016/j.exer.2016.04.010.
23.	Badea TC, Nathans J. Quantitative analysis of neuronal morphologies in the mouse retina visualized by using a genetically directed reporter[J]. J Comp Neurol, 2004, 480(4): 331-351. DOI: 10.1002/cne.20304.
24.	Jacoby J, Schwartz GW. Three small-receptive-field ganglion cells in the mouse retina are distinctly tuned to size, speed, and object motion[J]. J Neurosci, 2017, 37(3): 610-625. DOI: 10.1523/JNEUROSCI.2804-16.2016.
25.	Schmidt TM, Kofuji P. Functional and morphological differences among intrinsically photosensitive retinal ganglion cells[J]. J Neurosci, 2009, 29(2): 476-482. DOI: 10.1523/JNEUROSCI.4117-08.2009.
26.	Schmidt TM, Do MT, Dacey D, et al. Melanopsin-positive intrinsically photosensitive retinal ganglion cells: from form to function[J]. J Neurosci, 2011, 31(45): 16094-17101. DOI: 10.1523/JNEUROSCI.4132-11.2011.

1. Zhi Z, Pan M, Xie R, et al. The effect of temporal and spatial stimuli on the refractive status of guinea pigs following natural emmetropization[J]. Invest Ophthalmol Vis Sci, 2013, 54(1): 890-897. DOI: 10.1167/iovs.11-8064.
2. Ashby RS, Schaeffel F. The effect of bright light on lens compensation in chicks[J]. Invest Ophthalmol Vis Sci, 2010, 51(10): 5247-5253. DOI: 10.1167/iovs.09-4689.
3. Park SJ, Kim IJ, Looger LL, et al. Excitatory synaptic inputs to mouse on-off direction-selective retinal ganglion cells lack direction tuning[J]. J Neurosci, 2014, 34(11): 3976-3981. DOI: 10.1523/JNEUROSCI.5017-13.2014.
4. Freed MA. Asymmetry between ON and OFF alpha ganglion cells of mouse retina: integration of signal and noise from synaptic inputs[J]. J Physiol, 2017, 595(22): 6979-6991. DOI: 10.1113/JP274736.
5. Pickard GE, Sollars PJ. Intrinsically photosensitive retinal ganglion cells[J]. Rev Physiol Biochem Pharmacol, 2012, 162: 59-90. DOI: 10.1007/112_2011_4.
6. Pan F. Defocused image changes signaling of ganglion cells in the mouse retina[J/OL]. Cells, 2019, 8(7): 640[2019-06-26].http://www.mdpi.com/resolver?pii=cells8070640. DOI: 10.3390/cells8070640.
7. Mwachaka PM, Saidi H, Odula PO, et al. Effect of monocular deprivation on rabbit neural retinal cell densities[J]. J Ophthalmic Vis Res, 2015, 10(2): 144-150. DOI: 10.4103/2008-322X.163770.
8. Chakraborty R, Park HN, Hanif AM, et al. ON pathway mutations increase susceptibility to form-deprivation myopia[J]. Exp Eye Res, 2015, 137: 79-83. DOI: 10.1016/j.exer.2015.06.009.
9. Liu W, Khare SL, Liang X, et al. All Brn3 genes can promote retinal ganglion cell differentiation in the chick[J]. Development, 2000, 127(15): 3237-3247.
10. Turner EE, Jenne KJ, Rosenfeld MG. Brn-3.2: a Brn-3-related transcription factor with distinctive central nervous system expression and regulation by retinoic acid[J]. Neuron, 1994, 12(1): 205-218. DOI: 10.1016/0896-6273(94)90164-3.
11. Sengpiel F, Kind PC. The role of activity in development of the visual system[J]. Curr Biol, 2002, 12(23): 818-826. DOI: 10.1016/s0960-9822(02)01318-0.
12. Mui AM, Yang V, Aung MH, et al. Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina[J/OL]. PLoS One, 2018, 13(2): 0192435[2018-02-06].https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192435. DOI: 10.1371/journal.pone.0192435.
13. Cellerino AKohler K. Brain-derived neurotrophic factor/neurotrophin-4 receptor TrkB is localized on ganglion cells and dopaminergic amacrine cells in the vertebrate retina[J]. J Comp Neurol, 1997, 386(1): 149-160. DOI: 10.1002/(SICI)1096-9861(19970915)386:1<149::AID-CNE13>3.0.CO;2-F.
14. Chitranshi N, Dheer Y, Mirzaei M, et al. Loss of Shp2 rescues BDNF/TrkB signaling and contributes to improved retinal ganglion cell neuroprotection[J]. Mol Ther, 2019, 27(2): 424-441. DOI: 10.1016/j.ymthe.2018.09.019.
15. Xu L, Zhang Z, Xie T, et al. Inhibition of BDNF-AS provides neuroprotection for retinal ganglion cells against ischemic injury[J/OL]. PLoS One, 2016, 11(12): 0164941[2016-012-09]. http://dx.plos.org/10.1371/journal.pone.0164941. DOI: 10.1371/journal.pone.0164941.
16. Sanchez-Migallon MC, Valiente-Soriano FJ, Nadal-Nicolas FM, et al. Apoptotic retinal ganglion cell death after optic nerve transection or crush in mice: delayed RGC loss with BDNF or a caspase 3 inhibitor[J]. Invest Ophthalmol Vis Sci, 2016, 57(1): 81-93. DOI: 10.1167/iovs.15-17841.
17. Oshitari T, Yoshida-Hata N, Yamamoto S. Effect of neurotrophic factors on neuronal apoptosis and neurite regeneration in cultured rat retinas exposed to high glucose[J]. Brain Res, 2010, 1346: 43-51. DOI: 10.1016/j.brainres.2010.05.073.
18. Liang Y, Yu YH, Yu HJ, et al. Effect of BDNF-TrKB pathway on apoptosis of retinal ganglion cells in glaucomatous animal model[J]. Eur Rev Med Pharmacol Sci, 2019, 23(9): 3561-3568. DOI: 10.26355/eurrev_201905_17777.
19. Varella MH, de Mello FG, Linden R. Evidence for an antiapoptotic role of dopamine in developing retinal tissue[J]. J Neurochem, 1999, 73(2): 485-492. DOI: 10.1046/j.1471-4159.1999.0730485.x.
20. Dong J, Gao L, Han J, et al. Dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina independent of early synchronized spontaneous network activity[J]. Mol Neurobiol, 2017, 54(5): 3407-3417. DOI: 10.1007/s12035-016-9914-2.
21. Lin B, Wang SW. Masland RH retinal ganglion cell type, size, and spacing can be specified independent of homotypic dendritic contacts[J]. Neuron, 2004, 43(4): 475-485. DOI: 10.1016/j.neuron.2004.08.002.
22. Geeraerts E, Dekeyster E, Gaublomme D, et al. A freely available semi-automated method for quantifying retinal ganglion cells in entire retinal flatmounts[J]. Exp Eye Res, 2016, 147: 105-113. DOI: 10.1016/j.exer.2016.04.010.
23. Badea TC, Nathans J. Quantitative analysis of neuronal morphologies in the mouse retina visualized by using a genetically directed reporter[J]. J Comp Neurol, 2004, 480(4): 331-351. DOI: 10.1002/cne.20304.
24. Jacoby J, Schwartz GW. Three small-receptive-field ganglion cells in the mouse retina are distinctly tuned to size, speed, and object motion[J]. J Neurosci, 2017, 37(3): 610-625. DOI: 10.1523/JNEUROSCI.2804-16.2016.
25. Schmidt TM, Kofuji P. Functional and morphological differences among intrinsically photosensitive retinal ganglion cells[J]. J Neurosci, 2009, 29(2): 476-482. DOI: 10.1523/JNEUROSCI.4117-08.2009.
26. Schmidt TM, Do MT, Dacey D, et al. Melanopsin-positive intrinsically photosensitive retinal ganglion cells: from form to function[J]. J Neurosci, 2011, 31(45): 16094-17101. DOI: 10.1523/JNEUROSCI.4132-11.2011.

Chinese Journal of Ocular Fundus Diseases

The effect of form deprivation on the morphology of retinal ganglion cells in mice

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content