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T. Nakazawa, M. Ryu, T. Hisatomi, K. Noda, S. Nakao, M. Kayama, A. Hafezi-Moghadam, D. Vavvas, K. Nishida, J. W. Miller; The Role of Tnf in Photoreceptor Degeneration After Retinal Detachment; Suppression With Dexamethasone Treatment. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3718.
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© ARVO (1962-2015); The Authors (2016-present)
Photoreceptor degeneration is a major cause of visual loss in various retinal diseases. In this study, we investigated the role of anti-inflammatory treatment with dexamethasone (DEX) in retinal detachment (RD)-induced photoreceptor degeneration.
RD was caused by subretinal injection of hyaluronaic acid. Photoreceptor degeneration was assessed by counting the TdT-dUTP terminal nick-end labeling (TUNEL)-positive cells and by measuring the outer nuclear layer thickness after RD. To understand the role of anti-inflammatory treatment, DEX (1mg/kg, IP) or nano particle of poly (γ-glutamic acid) with DEX (NP-DEX, 0.8 mg/ul, subretinally) was injected just after RD. As the target of anti-inflammatory treatment, the expression of TNFα with or without DEX was examined by real-time PCR and RD was performed in mice deficient in TNFα or its receptors (TNFRI, TNFRII, TNFRI&II).
Treatment with DEX (p=0.0005) or NP-DEX (p=0.0065) significantly suppressed RD-induced photoreceptor degeneration and the expression of TNFα. RD-induced photoreceptor degeneration was significantly suppressed in mice deficient for TNFα (p<0.0001), TNFRII (p=0.001), or TNFRI&II (p<0.0001). However, lack of TNFRI did not protect from RD-induced photoreceptor degeneration (p=0.06).
Anti-inflammatory treatment with DEX had a neuroprotective effect against RD-induced photoreceptor degeneration. TNFα plays a critical role in RD-induced photoreceptor degeneration. This pathway may become an important target in the prevention of photoreceptor degeneration.
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