Photoreceptor necroptosis in experimental retinal detachment_Chinese Journal of Ocular Fundus Diseases

Authors：

Dongkai , ZhouEnliang , ZhuZicheng , 文磊 , 冯敬仰 , 闫泉 , 柯根杰 ,  孙晓东

Department of Ophthalmology, The Affiliated Anhui Provincial Hospital of Anhui Medical University, Hefei 230001, China;

Corresponding author：

孙晓东, Email: xiaoliuyu-079@163.com

Keywords：

Retinal detachment/physiopathology; Photoreceptor cells; Apoptosis; Animal experimentation

DOI：

10.3760/cma.j.issn.1005-1015.2014.04.011

Video：

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Objective To observe the morphological characteristics of photoreceptor necroptosis in experimental retinal detachment, and explore the mechanism. Methods A total of 60 Sprague-Dawley male rats were included in this study. Retinal detachment were induced in the right eyes with 1% sodium hyaluronate (50 μl) injection (experimental group), while the left eyes received no treatment (control group). At 3 days after modeling, the morphological characteristics of photoreceptor cell were observed by electron microscopy. Cleaved Caspase 8 and phosphorylation receptor-interacting protein 1 (p-RIP1) were measured by Western blot and immunoprecipitation. Results At 3 days after modeling, photoreceptor necroptosis showed the following morphological features: chromatin condensation, severe vacuolation, early loss of plasma membrane integrity, and many autophagosomes. Western blot showed that the protein expression of cleaved Caspase 8 were 0.78±0.03, 0.06±0.01 in experimental group and control group respectively, which was significantly different (F=4 023.21, P < 0.05). Immunoprecipitation showed that the protein expression of p-RIP1 were 0.23±0.03, 0.14±0.02 in experimental group and control group respectively, which was significantly different (F=56.44, P < 0.05). Conclusions Photoreceptor necroptosis showed chromatin condensation, severe vacuolation, early loss of plasma membrane integrity, and many autophagosomes. Necroptosis activation was associated with the increase of RIP1 phosphorylation.

Citation： Dongkai, ZhouEnliang, ZhuZicheng. Photoreceptor necroptosis in experimental retinal detachment. Chinese Journal of Ocular Fundus Diseases, 2014, 30(4): 378-380. doi: 10.3760/cma.j.issn.1005-1015.2014.04.011 Copy

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9.	孙晓东, 张皙, 俞彰.实验性视网膜脱离复位后的视网膜细胞超微结构观察[J].眼科研究, 2001, 19: 326-329.
10.	Kroemer G, Galluzzi L, Vandenabeele P, et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009[J]. Cell Death Differ, 2009, 16: 3-11.
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12.	Han W, Xie J, Li L, et al. Necrostatin-1 reverts shikonin-induced necroptosis to apoptosis[J]. Apoptosis, 2009, 14: 674-686.
13.	Hitomi J, Christofferson DE, Ng A, et al. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway[J]. Cell, 2008, 135: 1311-1323.
14.	Degterev A, Hitomi J, Germscheid M, et al. Identification of RIP1 kinase as a specific cellular target of necrostatins[J]. Nat Chem Biol, 2008, 4: 313-321.
15.	Liu H, Qian J, Wang F, et al. Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication[J]. Eye, 2010, 24: 137-144.
16.	Wang W, Wang F, Lu F, et al. The antiangiogenic effects of integrin alpha5beta1 inhibitor (ATN-161) in vitro and in vivo[J]. Invest Ophthalmol Vis Sci, 2011, 52: 7213-7220.
17.	Hisatomi T, Sakamoto T, Goto Y. Critical role of photoreceptor apoptosis in functional damage after retinal detachment[J]. Curr Eye Res, 2002, 24: 161-172.

1. Zacks DN, Boehlke C, Richards AL, et al. Role of the Fas-signaling pathway in photoreceptor neuroprotection[J]. Arch Ophthalmol, 2007, 125: 1389-1395.
2. Lo AC, Woo TT, Wong RL, et al. Apoptosis and other cell death mechanisms after retinal detachment: implications for photoreceptor rescue[J]. Ophthalmologica, 2011, 226 Suppl 1: S10-17.
3. Degterev A, Huang Z, Boyce M, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury[J]. Nat Chem Biol, 2005, 1: 112-119.
4. Dong K, Sun X. Targeting death receptor induced apoptosis and necroptosis: a novel therapeutic strategy to prevent neuronal damage in retinal detachment[J]. Med Hypotheses, 2011, 77: 144-146.
5. Dong K, Zhu H, Song Z, et al. Necrostatin-1 protects photoreceptors from cell death and improves functional outcome after experimental retinal detachment[J]. Am J Pathol, 2012, 181: 1634-1641.
6. Hisatomi T, Sakamoto T, Murata T, et al. Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by retinal detachment in vivo[J]. Am J Pathol, 2001, 158: 1271-1278.
7. Arimura N, Ki IY, Hashiguchi T, et al. Intraocular expression and release of high-mobility group box 1 protein in retinal detachment[J]. Lab Invest, 2009, 89: 278-289.
8. Mantopoulos D, Murakami Y, Comander J, et al. Tauroursodeoxycholic acid (TUDCA) protects photoreceptors from cell death after experimental retinal detachment[J/OL]. PLoS One, 2011, 6: 24245[2011-09-22]. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0024245.
9. 孙晓东, 张皙, 俞彰.实验性视网膜脱离复位后的视网膜细胞超微结构观察[J].眼科研究, 2001, 19: 326-329.
10. Kroemer G, Galluzzi L, Vandenabeele P, et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009[J]. Cell Death Differ, 2009, 16: 3-11.
11. Trichonas G, Murakami Y, Thanos A, et al. Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis[J]. Proc Natl Acad Sci USA, 2010, 107: 21695-21700.
12. Han W, Xie J, Li L, et al. Necrostatin-1 reverts shikonin-induced necroptosis to apoptosis[J]. Apoptosis, 2009, 14: 674-686.
13. Hitomi J, Christofferson DE, Ng A, et al. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway[J]. Cell, 2008, 135: 1311-1323.
14. Degterev A, Hitomi J, Germscheid M, et al. Identification of RIP1 kinase as a specific cellular target of necrostatins[J]. Nat Chem Biol, 2008, 4: 313-321.
15. Liu H, Qian J, Wang F, et al. Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication[J]. Eye, 2010, 24: 137-144.
16. Wang W, Wang F, Lu F, et al. The antiangiogenic effects of integrin alpha5beta1 inhibitor (ATN-161) in vitro and in vivo[J]. Invest Ophthalmol Vis Sci, 2011, 52: 7213-7220.
17. Hisatomi T, Sakamoto T, Goto Y. Critical role of photoreceptor apoptosis in functional damage after retinal detachment[J]. Curr Eye Res, 2002, 24: 161-172.

Chinese Journal of Ocular Fundus Diseases

Photoreceptor necroptosis in experimental retinal detachment

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