Effects of Cdk5 inhibitor Roscovitine on retinal degeneration in Royal College of Surgeons rat_Chinese Journal of Ocular Fundus Diseases

Authors：

RenYinghua , ZouGang , ZhangJinjin ,  盛迅伦

Department of Ophthalmology, Ningxia Eye Hospital, Ningxia People Hospital, Yinchuan 750001, China;

Corresponding author：

盛迅伦, Email: shengxunlun@163.com

Keywords：

Cyclin-dependent kinase 5/antagonists & inhibitors; Photoreceptor cells/pathology; Apoptosis; Animal experimentation

DOI：

10.3760/cma.j.issn.1005-1015.2015.03.013

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Objective To evaluate the photoreceptor-protective effects of Cdk5 inhibitor Roscovitine on retinal degeneration in Royal College of Surgeons (RCS) rat. Methods The RCS rats were divided into three groups according to postnatal days: the early (17 days), medium (25 days) and late intervention group (35 days). Cdk5 inhibitor Roscovitine were used in the right eyes by intravitreal injection as experimental eyes and Roscovitine solvent dimethylsulfoxide were used in the left as control at postnatal 17, 25, 35 days. Hematoxylin-eosin (HE) staining was used to observe the thickness of outer nuclear layer. The expression of Cdk5 P25 and cleave-caspase 3 in the retina was evaluated by immunohistochemistry. The protein expression of cleave-caspase 3 in the retina was determined by Western blot. The apoptosis of retinal cells was examined by terminal-deoxynucleotidyl transferase mediated nick end labeling. Results HE staining showed that thickness of outer nuclear layer in the early and medium intervention groups were significantly thicker than that in the control group (P < 0.05), particularly in the early intervention group. And there was no significant change in the late intervention group (P > 0.05). The expression level of Cdk5, p25, cleave-caspase 3 in the outer nuclear layer in three intervention groups were lower than that in the control group (P < 0.05), especially in the early intervention group. Conclusion Cdk5 inhibitor Roscovitine can delay the retinitis pigmentosa process in RCS rats by early, medium interventional therapy and may have a certain degree of photoreceptor-protective effects.

Citation： RenYinghua, ZouGang, ZhangJinjin. Effects of Cdk5 inhibitor Roscovitine on retinal degeneration in Royal College of Surgeons rat. Chinese Journal of Ocular Fundus Diseases, 2015, 31(3): 263-267. doi: 10.3760/cma.j.issn.1005-1015.2015.03.013 Copy

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1. Tso MO, Zhang C, Abler AS, et al. Apoptosis leads to photoreceptor degeneration in inherited retinal dystrophy of RCS rats[J]. Invest Ophthalmol Vis Sci, 1994, 35(6):2693-2699.
2. Hengartner MO. Death cycle and Swiss army knives[J]. Nature, 1998, 391(6666):441-442.
3. Zou H, Henzel WJ, Liu X, et al. Apaf1, a human protein homologous to C. elegans CED-4, participates in cytoch rome C-dependent activation of Caspase 3[J]. Cell, 1997, 90(3):405-413.
4. 张金金, 盛迅伦, 任英华.Cdk5/P25激酶活性与RCS大鼠视网膜神经细胞凋亡的关系[J].中华实验眼科杂志, 2013, 31(6):546-550.
5. 任英华, 盛迅伦, 张金金.等.细胞周期蛋白依赖激酶5与皇家外科学院大鼠视网膜色素变性发病过程中细胞凋亡的关系[J].中华眼底病杂志, 2013, 29(2):171-177.
6. Singer BF, Neugebauer NM, Forneirs J, et al. Locomotor conditioning by amphetamine requires cyclin-dependent kinase 5 signaling in the nucleus accumbens[J]. Neuropharmacology, 2014, 85:243-252.
7. 王悦, 张文婷, 张丽娜, 等.Alzhe imer病治疗新靶点Cdk5及其抑制剂的研究进展[J].中国药物化学杂志, 2009, 19(1):71-77.
8. Mary LM. Drugs targeting Alzheimer's disease:some things old and some things new[J].J Pharmacol Exp Ther, 2003, 304(3):897-904.
9. Menn B, Bach S, Blevins TL, et al. Delayed treatment with systemic (S)-roscovitine provides neuroprotection and inhibits in vivo CDK5 activity increase in animal stroke models[J/OL].PLoS One, 2010, 5(8):12117[2010-08-12].http://dx.plos.org/10.1371/journal.pone.0012117.
10. Zhang Q, Chen C, Lü J, et al. Cell cycle inhibition attenuates microglial proliferation and production of IL-1beta, MIP-1alpha, and NO after focal cerebral ischemia in the rat[J]. Glia, 2009, 57(8):908-920.
11. Camins A, Verdaguer E, Folch J, et al. The role of CDK5/p25 formation/inhibition in neurodegeneration[J]. Drug News Perspect, 2006, 19(8):453-460.
12. Zhang Q, Ahuja HS, Zakeri ZF, et al. Cyclin-dependent kinase 5 is associated with apoptotic cell death during development and tissue remodeling[J]. Dev Biol, 1997, 183(2):222-233.

Chinese Journal of Ocular Fundus Diseases

Effects of Cdk5 inhibitor Roscovitine on retinal degeneration in Royal College of Surgeons rat

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