The effects of FTY720 on retinal photoreceptor cells and microglial following light-induced degeneration in rat retina_Chinese Journal of Ocular Fundus Diseases

Authors：

HanBing ,  LiuSu

Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China;

Corresponding author：

LiuSu, Email: liusu2836@sina.com

Keywords：

Photic Stimulation/adverse effects; Microglia/physiology; Photoreceptor cells/physiology

DOI：

10.3760/cma.j.issn.1005-1015.2015.02.015

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effects of FTY720 on retinal photoreceptor cells and microglial following light-induced degeneration in rat retina. Methods 120 Sprague-Dawley rats were randomly divided into four groups including FTY720 group, solvent control group, model group and normal group. The rats of normal group were not intervened. The FTY720 group, solvent control group and model group establish retinal light injury mode. FTY720 was injected into abdominal cavity of the rats in FTY720 group 0.5 hours before light exposure. 50% dimethylsulfoxide was injected into abdominal cavity of the rats in solvent control group. The expressions of microglial cells in rat retinal were quantified using flow cytometry, the expressions of interleukin (IL)-1βwere examined by enzyme-linked immuno sorbent assay at 6 hours, 1 day, 3 days, 7 days after light exposure. The apoptosis of retinal photoreceptor cells were measured by terminal-deoxynucleoitidyl transferase mediated nick end labeling at 1 day after light exposure. The morphological change of retinal were viewed by haematoxylin and eosin staining at 7 days after light exposure. Results The expressions of microgilal and IL-1βbegan to rise at 1 day after light exposure, reached at peak at 3 days and decreased at 7 days. The expressions of IL-1βand microglial in FTY720 group were significantly lower than solvent control group and model group, but higher than normal group (P < 0.05).One day after exposure to light, the apoptosis cell ratio in normal group, model group, solvent control group and FTY720 group were 0, (87.66±2.50)%, (86.00±2.44)%, (49.66±2.80)%. The apoptosis cell in FTY720 group were higher than normal group, lower than solvent control group and model group (P < 0.05). Seven days after exposure to light, the retinal in normal group was structured and the cell was arranged well, the cell in solvent control group and model group was irregular arrangement and the outer nuclear layer (ONL) was thin after light exposure. The thickness of the ONL in FTY720 group was significantly higher than solvent control group and model group, below normal group. Conclusion FTY720 can prevents retinal photoreceptor cells from apoptosis and inhibits activation of microglial.

Citation： HanBing, LiuSu. The effects of FTY720 on retinal photoreceptor cells and microglial following light-induced degeneration in rat retina. Chinese Journal of Ocular Fundus Diseases, 2015, 31(2): 169-172. doi: 10.3760/cma.j.issn.1005-1015.2015.02.015 Copy

1.	Hoitsma AJ, Woodle ES, Abramowicz D, et al. FTY720 combined with tacrolimus in de novo renal transplantation:1-year, multicenter, open-label randomized study[J]. Nephrol Dial Transplant, 2011, 26(11):3802-3805.
2.	Yoshida Y, Tsuji T, Watanabe S, et al. Efficacy of combination treatment with fingolimod (FTY720) plus pathogenic autoantigen in a glucose-6-phosphate isomerase peptide (GPI325-339)-induced arthritis mouse model[J].Biol Pharm Bull, 2013, 36(11):1739-1746.
3.	Kong Y, Wang H, Wang S, et al.FTY720, a sphingosine-1 phosphate receptor modulator, improves liver fibrosis in a mouse model by impairing the motility of bone marrow-derived mesenchymal stem cells[J]. Inflammation, 2014, 37(4):1326-1336.
4.	Takasugi N, Sasaki T, Ebinuma I, et al.FTY720/fingolimod, a sphingosine analogue, reduces amyloid-beta production in neurons. PLoS One, 2013, 8(5):64050. http://dx.plos.org/10.1371/journal.pone.0064050.
5.	Noda H, Takeuchi H, Mizuno T. Fingolimod phosphate promotes the neuroprotective effects of microglia[J]. J Neuroimmunol, 2013, 256(1-2):13-18.
6.	Collier RJ, Wang Y, Smith SS, et al. Complement deposition and microglial activation in the outer retina in light-induced retinopathy:inhibition by a 5-HT1A agonist[J]. Invest Ophthalmol Vis Sci, 2011, 52(11):8108-8116.
7.	Ciesek S, Steinmann E, Manns MP, et al. The suppressive effect that myriocin has on hepatitis C virus RNA replication is independent of inhibition of serine palmitoyl transferase[J]. J Infect Dis, 2008, 198(7):1091-1093.
8.	Qin X, Yue Z, Sun B, et al. Sphingosine and FTY720 are potent inhibitors of the transient receptor potential melastatin 7 (TRPM7) channels[J]. Br J Pharmacol, 2013, 168(6):1294-1312.
9.	Paugh SW, Cassidy MP, He H, et al. Sphingosine and its analog, the immunosuppressant 2-amino-2-(2-ethyl)-1, 3-propanediol, interact with the CB1 cannabinoid receptor[J]. Mol Pharmacol, 2006, 70(1):41-50.
10.	Wang X, Fan J, Zhang M. Upregulation of SOX9 in Glial (Müller) cells in retinal light damage of rats[J]. Neurosci Lett, 2013, 556:140-145.
11.	Tian L, Zhang L, Xia F. Hydrogen-rich saline ameliorates[J].Med Gas Res, 2013, 3(1):19.
12.	Tanito M, Li F, Anderson RE. Protection of retinal pigment epithelium by OT-551 and its metabolite TEMPOL-H against light-induced damage in rats[J]. Exp Eye Res, 2010, 91(1):111-114.
13.	倪颖勤, 姜春晖, 徐格致.大鼠视网膜光损伤模型中小胶质细胞的迁移及活化[J].复旦学报(医学版), 2011, 38(2):126-130, 135.
14.	Zeng HY. Identification of sequential events and factors associated with microglial activation, migration, and cytotoxicity in retinal degeneration in rd mice[J]. Invest Ophthalmol Vis Sci, 2005, 46(8):2992-2999.
15.	Liu Y, Yang X, Utheim TP, et al. Correlation of cytokine levels and microglial cell infiltration during retinal degeneration in RCS rats. PLoS One, 2013, 8(12):82061. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082061..
16.	Ni YQ, Xu GZ, Hu WZ, et al. Neuroprotective effects of naloxone against light-induced photoreceptor degeneration through inhibiting retinal microglial activation[J]. Invest Ophthalmol Vis Sci, 2008, 49(6):2589-2598.
17.	Kitaoka S, Furuyashiki T. Roles of inflammation-related molecules in emotional changes induced by repeated stress[J]. Nihon Shinkei Seishin Yakurigaku Zasshi, 2014, 34(4):109-115.
18.	Smith JA, Das A, Ray SK, et al. Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases[J]. Brain Res Bull, 2012, 87(1):10-20.

1. Hoitsma AJ, Woodle ES, Abramowicz D, et al. FTY720 combined with tacrolimus in de novo renal transplantation:1-year, multicenter, open-label randomized study[J]. Nephrol Dial Transplant, 2011, 26(11):3802-3805.
2. Yoshida Y, Tsuji T, Watanabe S, et al. Efficacy of combination treatment with fingolimod (FTY720) plus pathogenic autoantigen in a glucose-6-phosphate isomerase peptide (GPI325-339)-induced arthritis mouse model[J].Biol Pharm Bull, 2013, 36(11):1739-1746.
3. Kong Y, Wang H, Wang S, et al.FTY720, a sphingosine-1 phosphate receptor modulator, improves liver fibrosis in a mouse model by impairing the motility of bone marrow-derived mesenchymal stem cells[J]. Inflammation, 2014, 37(4):1326-1336.
4. Takasugi N, Sasaki T, Ebinuma I, et al.FTY720/fingolimod, a sphingosine analogue, reduces amyloid-beta production in neurons. PLoS One, 2013, 8(5):64050. http://dx.plos.org/10.1371/journal.pone.0064050.
5. Noda H, Takeuchi H, Mizuno T. Fingolimod phosphate promotes the neuroprotective effects of microglia[J]. J Neuroimmunol, 2013, 256(1-2):13-18.
6. Collier RJ, Wang Y, Smith SS, et al. Complement deposition and microglial activation in the outer retina in light-induced retinopathy:inhibition by a 5-HT1A agonist[J]. Invest Ophthalmol Vis Sci, 2011, 52(11):8108-8116.
7. Ciesek S, Steinmann E, Manns MP, et al. The suppressive effect that myriocin has on hepatitis C virus RNA replication is independent of inhibition of serine palmitoyl transferase[J]. J Infect Dis, 2008, 198(7):1091-1093.
8. Qin X, Yue Z, Sun B, et al. Sphingosine and FTY720 are potent inhibitors of the transient receptor potential melastatin 7 (TRPM7) channels[J]. Br J Pharmacol, 2013, 168(6):1294-1312.
9. Paugh SW, Cassidy MP, He H, et al. Sphingosine and its analog, the immunosuppressant 2-amino-2-(2-ethyl)-1, 3-propanediol, interact with the CB1 cannabinoid receptor[J]. Mol Pharmacol, 2006, 70(1):41-50.
10. Wang X, Fan J, Zhang M. Upregulation of SOX9 in Glial (Müller) cells in retinal light damage of rats[J]. Neurosci Lett, 2013, 556:140-145.
11. Tian L, Zhang L, Xia F. Hydrogen-rich saline ameliorates[J].Med Gas Res, 2013, 3(1):19.
12. Tanito M, Li F, Anderson RE. Protection of retinal pigment epithelium by OT-551 and its metabolite TEMPOL-H against light-induced damage in rats[J]. Exp Eye Res, 2010, 91(1):111-114.
13. 倪颖勤, 姜春晖, 徐格致.大鼠视网膜光损伤模型中小胶质细胞的迁移及活化[J].复旦学报(医学版), 2011, 38(2):126-130, 135.
14. Zeng HY. Identification of sequential events and factors associated with microglial activation, migration, and cytotoxicity in retinal degeneration in rd mice[J]. Invest Ophthalmol Vis Sci, 2005, 46(8):2992-2999.
15. Liu Y, Yang X, Utheim TP, et al. Correlation of cytokine levels and microglial cell infiltration during retinal degeneration in RCS rats. PLoS One, 2013, 8(12):82061. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082061..
16. Ni YQ, Xu GZ, Hu WZ, et al. Neuroprotective effects of naloxone against light-induced photoreceptor degeneration through inhibiting retinal microglial activation[J]. Invest Ophthalmol Vis Sci, 2008, 49(6):2589-2598.
17. Kitaoka S, Furuyashiki T. Roles of inflammation-related molecules in emotional changes induced by repeated stress[J]. Nihon Shinkei Seishin Yakurigaku Zasshi, 2014, 34(4):109-115.
18. Smith JA, Das A, Ray SK, et al. Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases[J]. Brain Res Bull, 2012, 87(1):10-20.

Chinese Journal of Ocular Fundus Diseases

The effects of FTY720 on retinal photoreceptor cells and microglial following light-induced degeneration in rat retina

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content