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Tumor necrosis factor-alpha mediates photoreceptor death in a rodent model of retinal detachment.

Authors: Nakazawa, T  Kayama, M  Ryu, M  Kunikata, H  Watanabe, R  Yasuda, M  Kinugawa, J  Vavvas, D  Miller, JW 
Citation: Nakazawa T, etal., Invest Ophthalmol Vis Sci. 2011 Mar 14;52(3):1384-91. Print 2011 Mar.
Pubmed: (View Article at PubMed) PMID:21402953
DOI: Full-text: DOI:10.1167/iovs.10-6509

PURPOSE: Photoreceptor degeneration is a major cause of visual loss in various retinal diseases, including retinal detachment (RD) and neovascular AMD, but the underlying mechanisms remain elusive. In this study, the role of TNFalpha in RD-induced photoreceptor degeneration was investigated. METHODS: RD was induced by subretinal injection of hyaluronic acid. Photoreceptor degeneration was assessed by counting the number of apoptotic cells with TdT-dUTP terminal nick-end labeling (TUNEL) 3 days after RD and measurement of the outer nuclear layer (ONL) thickness 7 days after RD. As the target of anti-inflammatory treatment, the expression of TNFalpha, with or without dexamethasone (DEX) was examined in rats by real-time PCR. To understand the role of TNFalpha in photoreceptor degeneration, RD was induced in mice deficient in TNFalpha or its receptors (TNFR1, TNFR2, and TNFR1 and -2), or in wild-type (WT) mice by using a functionally blocking antibody to TNFalpha. CD11b(+) cells in the outer plexiform layer (OPL) and subretinal space were counted by immunohistochemistry (IHC). RESULTS: Treatment with DEX (P = 0.001) significantly suppressed RD-induced photoreceptor degeneration and the expression of TNFalpha. RD-induced photoreceptor degeneration was significantly suppressed with specific blockade of TNFalpha (P = 0.032), in mice deficient for TNFalpha (P < 0.001), TNFR2 (P = 0.001), or TNFR1 and -2 (P < 0.001). However, lack of TNFR1 did not protect against RD-induced photoreceptor degeneration (P = 0.060). Muller cell activation was unchanged in WT and TNFalpha(-/-) mice. Recruitment of CD11b(+) monocytes was significantly lower in the TNFalpha(-/-) mice compared to WT mice (P = 0.002). CONCLUSIONS: TNFalpha plays a critical role in RD-induced photoreceptor degeneration. This pathway may become an important target in the prevention of RD-induced photoreceptor degeneration.

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RGD Object Information
RGD ID: 5131257
Created: 2011-04-26
Species: All species
Last Modified: 2011-04-26
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.