Effect of the Notch signaling pathway on retinal ganglion cells and its neuroprotection in rats with acute ocular hypertension

被引:5
作者
Li, Lei [1 ,2 ]
Chen, Li-Ping [2 ]
Liu, Qing-Huai [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanjing 210029, Jiangsu, Peoples R China
[2] Hainan Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Haikou 570102, Hainan, Peoples R China
关键词
Notch signaling pathway; ocular hypertension; retinal ganglion cells; anti-apoptotic; neuroprotection; growth-associated protein; ISCHEMIA-REPERFUSION INJURY; INTRAOCULAR-PRESSURE; CEREBRAL-ISCHEMIA; ACTIVATION; GLAUCOMA; MODEL; MICE; DIFFERENTIATION; NEUROGENESIS; DEGENERATION;
D O I
10.18240/ijo.2018.02.05
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
AIM: To explore the effect of the Notch signaling pathway on retinal ganglion cells (RGCs) and optic nerve in rats with acute ocular hypertension (OH). METHODS: Totally 48 Sprague-Dawley (SD) rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 mu L phosphate buffered solution (PBS) and another group of OH rats received a single intravitreal injection of 10 mu mol/L gamma-secretase inhibitor (DAPT). Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were adopted to determine the mRNA level of Notch and the protein levels of Notch, Bcl-2, Bax, caspase-3, and growth-associated protein 43 (GAP-43). The RGC apoptosis conditions were assessed by TUNEL staining. RESULTS: The OH rats and PBS-injected rats had increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, with severer macular edema and RGCs more loosely aligned, when compared with the normal rats. The DAPT-treated rats displayed increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, in comparison with the OH rats and PBS-injected rats. RGCs were hardly observed and macular edema became severe in the DAPT-treated rat. CONCLUSION: The Notch signaling pathway may suppress the apoptosis of retinal ganglion cells and enhances the regeneration of the damaged optic nerves in rats with acute OH.
引用
收藏
页码:208 / 215
页数:8
相关论文
共 42 条
  • [1] Delta-1 is a regulator of neurogenesis in the vertebrate retina
    Ahmad, I
    Dooley, CM
    Polk, DL
    [J]. DEVELOPMENTAL BIOLOGY, 1997, 185 (01) : 92 - 103
  • [2] Notch signaling: simplicity in design, versatility in function
    Andersson, Emma R.
    Sandberg, Rickard
    Lendahl, Urban
    [J]. DEVELOPMENT, 2011, 138 (17): : 3593 - 3612
  • [3] Gamma secretase-mediated notch signaling worsens brain damage and functional outcome in ischemic stroke
    Arumugam, TV
    Chan, SL
    Jo, DG
    Yilmaz, G
    Tang, SC
    Cheng, AW
    Gleichmann, M
    Okun, E
    Dixit, VD
    Chigurupati, S
    Mughal, MR
    Ouyang, X
    Miele, L
    Magnus, T
    Poosala, S
    Granger, DN
    Mattson, MP
    [J]. NATURE MEDICINE, 2006, 12 (06) : 621 - 623
  • [4] AUSTIN CP, 1995, DEVELOPMENT, V121, P3637
  • [5] Calaza KD, 2010, AN ACAD BRAS CIENC, V82, P595, DOI 10.1590/S0001-37652010000300007
  • [6] Evaluation of potential topical and systemic neuroprotective agents for ocular hypertension-induced retinal ischemia-reperfusion injury
    Chen, Yi-Ing
    Lee, Yih-Jing
    Wilkie, David A.
    Lin, Chung-Tien
    [J]. VETERINARY OPHTHALMOLOGY, 2014, 17 (06) : 432 - 442
  • [7] Thermosensitive chitosan-based hydrogel as a topical ocular drug delivery system of latanoprost for glaucoma treatment
    Cheng, Yung-Hsin
    Tsai, Tung-Hu
    Jhan, Yong-Yu
    Chiu, Allen Wen-hsiang
    Tsai, Kun-Ling
    Chien, Chian-Shiu
    Chiou, Shih-Hwa
    Liu, Catherine Jui-Lin
    [J]. CARBOHYDRATE POLYMERS, 2016, 144 : 390 - 399
  • [8] Chiu Kin, 2009, J Ocul Biol Dis Infor, V2, P127
  • [9] Functional Circuitry of the Retina
    Demb, Jonathan B.
    Singer, Joshua H.
    [J]. ANNUAL REVIEW OF VISION SCIENCE, VOL 1, 2015, 1 : 263 - 289
  • [10] Postnatal dysregulation of Notch signal disrupts dendrite development of adult-born neurons in the hippocampus and contributes to memory impairment
    Ding, Xue-Feng
    Gao, Xiang
    Ding, Xin-Chun
    Fan, Ming
    Chen, Jinhui
    [J]. SCIENTIFIC REPORTS, 2016, 6