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J Mol Neurosci (2014) 54:243251 DOI 10.1007/s12031-014-0281-z
Ras Homolog Enriched in the Brain is Linked to Retinal Ganglion Cell Apoptosis after Light Injury in Rats
Qinmeng Shu & Yue Xu & Hong Zhuang & Jiawen Fan &
Zhongcui Sun & Meng Zhang & Gezhi Xu
Received: 19 October 2013 /Accepted: 3 March 2014 /Published online: 25 March 2014 # Springer Science+Business Media New York 2014
Abstract Ras homolog enriched in the brain (Rheb) is a small GTPase of the Ras family. It has been confirmed that Rheb activation not only regulates cell growth and migration but also induces neuron apoptosis after toxic stimuli. However, the function of Rheb in the retina is still not fully understood. To find out whether Rheb was involved in retinal neuron death, the expression profile of Rheb in light-damaged retinal ganglion cells (RGCs) of adult rats was investigated. Western blotting showed the expression of Rheb was significantly upregulated in the injured retina. Rheb was mainly detected in apoptotic RGCs by using double immunofluorescent staining. Active caspase-3 was upregulated and co-labeled with Rheb. Meanwhile, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) showed that Rheb-positive RGCs underwent apoptosis after light exposure, which suggested that Rheb might be relevant to RGC apoptosis following phototoxicity. Furthermore, Western blotting and immunofluorescence showed that the expression profiles of CyclinD1 and cyclin-dependent kinase 4 (CDK4) were parallel with that of Rheb in a timespace dependent manner. Based on this study, it is speculated that Rheb might play an important role in physiological and pathological
process in light-induced retina damage, which might provide a potential therapeutic avenue of retinal degeneration.
Keywords Rheb . Retinal ganglion cells . Neuronal apoptosis . Light-induced retinal damage . Rat
Introduction
Age-related macular degeneration (AMD) is one of the major sight-threatening diseases in developed countries. The severe visual loss caused by AMD is affecting roughly 10 % of the USA and European populations over the age of 70 (Augood et al. 2006; Friedman et al. 2004; Rein et al. 2009; Smith et al. 2001). The underlying mechanism of AMD remains elusive. Multiple causative factors, such as smoking, genetic background, age, and antioxidant deficiency, have been described in the etiology of AMD (Lim et al. 2012; Randazzo et al. 2011; Seddon et al. 2011)....