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

Toru Nakazawa, Maki Kayama, Morin Ryu, Hiroshi Kunikata, Ryou Watanabe, Masayuki Yasuda, Jiro Kinugawa, Demetrios Vavvas, Joan W. Miller

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

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 TNFα 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 nickend 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 TNFα, with or without dexamethasone (DEX) was examined in rats by real-time PCR. To understand the role of TNFα in photoreceptor degeneration, RD was induced in mice deficient in TNFα or its receptors (TNFR1, TNFR2, and TNFR1 and -2), or in wild-type (WT) mice by using a functionally blocking antibody to TNFα. 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 TNFα. RD-induced photoreceptor degeneration was significantly suppressed with specific blockade of TNFα (P = 0.032), in mice deficient for TNFα (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). Müller cell activation was unchanged in WT and TNFα -/- mice. Recruitment of CD11b + monocytes was significantly lower in the TNFα -/- mice compared to WT mice (P = 0.002). CONCLUSIONS. TNFα plays a critical role in RD-induced photoreceptor degeneration. This pathway may become an important target in the prevention of RD-induced photoreceptor degeneration.

Original languageEnglish
Pages (from-to)1384-1391
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number3
DOIs
Publication statusPublished - 2011 Mar

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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