RTP801 gene expression is differentially upregulated in retinopathy and is silenced by PF-04523655, a 19-mer siRNA directed against RTP801

Investigative Ophthalmology and Visual Science

Volumn 55, Issue 3, 2013, Pages 1232-1240

  Rittenhouse, Kay D ^a   Johnson, Theodore R ^a   Vicini, Paolo ^a   Hirakawa, Brad ^a   Kalabat, Dalia ^a   Yang, Amy H ^a   Huang, Wenhu ^a   Basile, Anthony S ^a,b  

^a PFIZER INC   (United States)

^b ALLERGAN INC   (United States)

Author keywords

Gene expression; Hypoxia; PK PD; Retinal ischemia; Retinal pigment epithelium

Indexed keywords

PF 04523655; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; COLORIMETRY; CONTROLLED STUDY; DIABETIC RETINOPATHY; GENE EXPRESSION; INCIDENCE; LASER CAPTURE MICRODISSECTION; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; RETINA; RETINOPATHY; SUBRETINAL NEOVASCULARIZATION; UPREGULATION;

GENE EXPRESSION, PK/PD, HYPOXIA, RETINAL PIGMENT EPITHELIUM, RETINAL ISCHEMIA;

ANIMALS; DIABETIC RETINOPATHY; DISEASE MODELS, ANIMAL; POLYMERASE CHAIN REACTION; RATS; RATS, LONG-EVANS; REPRESSOR PROTEINS; RETINAL PIGMENT EPITHELIUM; RNA, MESSENGER; RNA, SMALL INTERFERING; UP-REGULATION;

EID: 84895748628     PISSN: 01460404     EISSN: 15525783     Source Type: Journal    
DOI: 10.1167/iovs.13-13449     Document Type: Article

References (24)

1. Tolentino MJ, Brucker AJ, Fosnot J, et al. Intravitreal injection of vascular endothelial growth factor small interfering RNA inhibits growth and leakage in a nonhuman primate, laserinduced model of choroidal neovascularization. Retina. 2004; 24:132-138.
2. Nguyen QD, Schachar RA, Nduaka CI, et al. MONET Clinical Study Group. Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study). Ophthalmol. 2012; 119:1867-1873.
3. Nguyen QD, Schachar RA, Nduaka CI, et al. Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS Study). Invest Ophthalmol Vis Sci. 2012;53:7666-7674.
4. Kaiser PK, Symons RC, Shah SM, et al. RNAi-based treatment for neovascular age-related macular degeneration by Sirna-027. Am J Ophthalmol. 2010;150:33-39.
5. Corradetti MN, Inoki K, Guan KL. The stress-induced proteins RTP801 and RTP801L are negative regulators of the mammalian target of rapamycin pathway. J Biol Chem. 2005;280: 9769-9772.
6. Brugarolas J, Lei K, Hurley RL, et al. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev. 2004;18:2893-2904.
7. Ellisen LW. Smoking and emphysema: the stress connection. Nat Medicine. 2010;16:754-755.
8. Shoshani T, Faerman A, Mett I, et al. Identification of a novel HIF 1-responsive gene, RTP801, involved in apoptosis. Mol Cell Biol. 2002;22:2283-2293.
9. Ellisen LW, Ramsayer KD, Johannessen CM, et al. REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen species. Mol Cell. 2002;10:995-1005.
10. Lee DU, Huang W, Rittenhouse KD, Jessen B. Retina expression and cross-species validation of gene silencing by PF-655, a small interfering RNA against RTP801 for the treatment of ocular disease. J Ocul Pharmacol Ther. 2012; 28:222-230.
11. Malagelada C, Zong HJ, Lloyd AG. RTP801 is induced in Parkinson's disease and mediates neuron death by inhibiting Akt phosphorylation/activation. J Neurosci. 2008;28:14363-14371.
12. Malagelada C, Elizabeth JR, Biswas SC, et al. RTP801 is elevated in Parkinson brain substantia nigral neurons and mediates death in cellular modes of Parkinson's diseases by a mechanism involving mTOR inactivation. J Neurosci. 2006; 26:9996-10005.
13. Yoshida T, Mett I, Bhunia AK, et al. RTP801, a suppressor of mTOR signaling, is an essential mediator of cigarette smoke-induced pulmonary injury and emphysema. Nat Med. 2010; 16:767-773.
14. Lang CH, Frost RA, Vary TC. Acute alcohol intoxication increases REDD1 in skeletal muscle. Alcohol Clin Exp Res. 2008;32:796-805.
15. Sim DA, Keane PA, Zarranz-Ventura J, et al. The effects of macular ischemia on visual acuity in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2013;54:2353-2360.
16. Xu H, Chen M, Forrester JV. Para-inflammation in the aging retina. Prog Retin Eye Res. 2009;28:348-368.
17. Klein R, Klein BE, Knudtson MD, Wong TY, Shankar A, Tsai MY. Systemic markers of inflammation, endothelial dysfunction, and age-related maculopathy. Am J Ophthalmol. 2005; 140:35-44.
18. Brafman A, Mett I, Shafir M, et al. Inhibition of oxygen-induced retinopathy in RTP801 deficient mice. Invest Ophthalmol Vis Sci. 2004;15:3796-3805.
19. Phase II Open Label Multicenter Study For Age Related Macular Degeneration Comparing PF-04523655 Versus Lucentis In The Treatment Of Subjects With CNV (MONET Study). Available at: ClinicalTrials. gov. Identifier: NCT00713518.
20. Gabrielsson J, Weiner D. Effect-Compartment Model in Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications. 2nd ed. Stockholm, Sweden: Swedish Pharmaceutical Press; 1997:210-222.
21. Turabelidze A, Guo S, DiPietro LA. Importance of Housekeeping gene selection for accurate RT-qPCR in a wound healing model. Wound Repair Regen. 2010;18:460-466.
22. Van den Berg A, Mols J, Han J. RISC-target interaction: cleavage and translational suppression. Biochimt Biophys Acta. 2008; 1779:668-677.
23. Bartlett DW, Davis ME. Insights into the kinetics of siRNAmediated gene silencing from live-cell and live-animal bioluminescent imaging. Nucleic Acids Res. 2006;34:322-333.
24. Léveillard T, Mohand-Saïd S, Lorentz O, et al. Identification and characterization of rod-derived cone viability factor. Nat Genet. 2004;36:755-759.