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Differential neuronal expression of receptor interacting protein 3 in rat retina: involvement in ischemic stress response

Ju-Fang Huang1, Lei Shang1, Meng-Qi Zhang2, Hui Wang1, Dan Chen1, Jian-Bin Tong1, He Huang3, Xiao-Xin Yan1, Le-Ping Zeng1 and Kun Xiong1*

Author Affiliations

1 Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, 410013, China

2 Eight-year Clinical Medicine Program, Class 2002, Central South University Xiangya School of Medicine, Changsha, Hunan, 410013, China

3 Department of Histology and Embrology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, 410013, China

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BMC Neuroscience 2013, 14:16  doi:10.1186/1471-2202-14-16

Published: 2 February 2013



Receptor-interacting protein 3 (RIP3), a member of RIP family proteins, has been shown to participate in programmed necrosis or necroptosis in cell biology studies. Evidence suggests that necroptosis may be a mode of neuronal death in the retina.


In the present study we determined the expression of RIP3 in normal rat retina and its changes following acute high intraocular pressure (aHIOP). RIP3 immunoreactivity (IR) was largely present in the inner retinal layers, localized to subsets of cells expressing neuron-specific nuclear antigen (NeuN), parvalbumin and calbindin in the ganglion cell layer (GCL) and inner nuclear layer (INL). No double labeling was detected for RIP3 with PKC-α or rhodopsin. RIP3 immunoreactivity was increased in the GCL at 6 hr and 12 hr, but reduced at 24 hr in the retina, without apparent alteration in laminar or cellular distribution pattern. Western blot analysis confirmed the above time-dependent alteration in RIP3 protein expression. RIP3 expressing cells frequently co-localized with propidium iodide (PI). A few co-localized cells were observed between RIP3 and Bax or cleaved caspase-3 in the GCL in 12 hr following aHIOP.


The results indicate that RIP3 is expressed differentially in retinal neurons in adult rats, including subsets of ganglion cells, amacrine and horizontal cells. RIP3 protein levels are elevated rapidly following aHIOP. RIP3 labeling co-localized with PI, Bax or cleaved caspase-3 among cells in the ganglion cell layer following aHIOP, which suggest its involvement of RIP3 in neuronal responses to acute ischemic insults.

Receptor-interacting protein 3; Retina; Necroptosis; aHIOP