Neuroprotective and antioxidant effects of ghrelin in an experimental glaucoma model

被引:28
作者
Can, Nagehan [1 ]
Catak, Onur [2 ]
Turgut, Burak [2 ]
Demir, Tamer [2 ]
Ilhan, Nevin [3 ]
Kuloglu, Tuncay [4 ]
Ozercan, Ibrahim Hanifi [5 ]
机构
[1] Elazig Training & Res Hosp, Dept Ophthalmol, TR-23119 Elazig, Turkey
[2] Firat Univ, Sch Med, Dept Ophthalmol, TR-23119 Elazig, Turkey
[3] Firat Univ, Sch Med, Dept Biochem, TR-23119 Elazig, Turkey
[4] Firat Univ, Sch Med, Dept Histol & Embryol, TR-23119 Elazig, Turkey
[5] Firat Univ, Sch Med, Dept Pathol, TR-23119 Elazig, Turkey
来源
DRUG DESIGN DEVELOPMENT AND THERAPY | 2015年 / 9卷
关键词
experimental glaucoma; ganglion cells; ghrelin; neuroprotective; antioxidant; NITRIC-OXIDE SYNTHASE; RETINAL GANGLION-CELLS; NECROSIS-FACTOR-ALPHA; OPEN-ANGLE GLAUCOMA; OPTIC-NERVE; OXIDATIVE STRESS; RAT MODEL; INTRAOCULAR-PRESSURE; INHIBITS APOPTOSIS; MULLER CELL;
D O I
10.2147/DDDT.S83067
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Damage to retinal ganglion cells due to elevation of intraocular pressure (IOP) is responsible for vision loss in glaucoma. Given that loss of these cells is irreversible, neuroprotection is crucial in the treatment of glaucoma. In this study, we investigated the possible antioxidant and neuroprotective effects of ghrelin on the retina in an experimental glaucoma model. Twenty-one Sprague-Dawley rats were randomly assigned to three groups comprising seven rats each. The rats in the control group were not operated on and did not receive any treatment. In all rats in the other groups, IOP was increased by cauterization of the limbal veins. After creation of the IOP increase, saline 1 mL/kg or ghrelin 40 mu g/kg was administered intraperitoneally every day for 14 days in the vehicle control group and ghrelin groups, respectively. On day 14 of the study, the eyes were enucleated. Levels of malondialdehyde (MDA), nitric oxide (NO), and nitric oxide synthase-2 (NOS2) in anterior chamber fluid were measured. The retinas were subjected to immunohistochemistry staining for glial fibrillary acidic protein (GFAP), S-100, and vimentin expression. Mean levels of MDA, NO, and NOS2 in the aqueous humor were higher in the vehicle control group than in the control group (P<0.05). Mean levels of MDA, NO, and NOS2 in the ghrelin group did not show a significant increase compared with levels in the control group (P>0.05). Retinal TUNEL and immunohistochemistry staining in the vehicle control group showed an increase in apoptosis and expression of GFAP, S-100, and vimentin compared with the control group (P<0.05). In the ghrelin group, apoptosis and expression of GFAP, S-100, and vimentin was significantly lower than in the vehicle control group (P<0.05). This study suggests that ghrelin has antioxidant and neuroprotective effects on the retina in an experimental glaucoma model.
引用
收藏
页码:2819 / 2829
页数:11
相关论文
共 65 条
  • [1] Nitric oxide synthases: structure, function and inhibition
    Alderton, WK
    Cooper, CE
    Knowles, RG
    [J]. BIOCHEMICAL JOURNAL, 2001, 357 (03) : 593 - 615
  • [2] The extra-hypothalamic actions of ghrelin on neuronal function
    Andrews, Zane B.
    [J]. TRENDS IN NEUROSCIENCES, 2011, 34 (01) : 31 - 40
  • [3] Ghrelin Promotes and Protects Nigrostriatal Dopamine Function via a UCP2-Dependent Mitochondrial Mechanism
    Andrews, Zane B.
    Erion, Derek
    Beiler, Rudolph
    Liu, Zhong-Wu
    Abizaid, Alfonso
    Zigman, Jeffrey
    Elsworth, John D.
    Savitt, Joseph M.
    DiMarchi, Richard
    Tschoep, Matthias
    Roth, Robert H.
    Gao, Xiao-Bing
    Horvath, Tamas L.
    [J]. JOURNAL OF NEUROSCIENCE, 2009, 29 (45) : 14057 - 14065
  • [4] The role of nitric oxide in the inhibitory effect of ghrelin against penicillin-induced epileptiform activity in rat
    Aslan, Ali
    Yildirim, Mehmet
    Ayyildiz, Mustafa
    Guven, Ayla
    Agar, Erdal
    [J]. NEUROPEPTIDES, 2009, 43 (04) : 295 - 302
  • [5] Nitrotyrosine formation and apoptosis in rat models of ocular injury
    Aslan, M
    Yücel, I
    Akar, Y
    Yücel, G
    Çiftçioglu, MA
    Sanlioglu, S
    [J]. FREE RADICAL RESEARCH, 2006, 40 (02) : 147 - 153
  • [6] Aydin S., 2006, Turkiye Klinikleri tip Bilimleri Dergisi, V26, P272
  • [7] BABIZHAYEV MA, 1989, ACTA OPHTHALMOL, V67, P371
  • [8] Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT
    Baldanzi, G
    Filigheddu, N
    Cutrupi, S
    Catapano, F
    Bonissoni, S
    Fubini, A
    Malan, D
    Baj, G
    Granata, R
    Broglio, F
    Papotti, M
    Surico, N
    Bussolino, F
    Isgaard, J
    Deghenghi, R
    Sinigaglia, F
    Prat, M
    Muccioli, G
    Ghigo, E
    Graziani, A
    [J]. JOURNAL OF CELL BIOLOGY, 2002, 159 (06) : 1029 - 1037
  • [9] S100-BETA PROTECTS HIPPOCAMPAL-NEURONS FROM DAMAGE-INDUCED BY GLUCOSE DEPRIVATION
    BARGER, SW
    VANELDIK, LJ
    MATTSON, MP
    [J]. BRAIN RESEARCH, 1995, 677 (01) : 167 - 170
  • [10] MACROPHAGES, MICROGLIA, AND ASTROCYTES ARE RAPIDLY ACTIVATED AFTER CRUSH INJURY OF THE GOLDFISH OPTIC-NERVE - A LIGHT AND ELECTRON-MICROSCOPIC ANALYSIS
    BATTISTI, WP
    WANG, J
    BOZEK, K
    MURRAY, M
    [J]. JOURNAL OF COMPARATIVE NEUROLOGY, 1995, 354 (02) : 306 - 320