Purchase this article with an account.
T. Nakazawa, T. Hisatomi, K. Noda, S. Nakao, A. Hafezi-Moghadam, K. Nishida, J. W. Miller; TNF Mediates Retinal Detachment-Induced Photoreceptor Loss. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4512.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Photoreceptor degeneration is a major cause of visual loss in various retinal diseases, including retinal detachment (RD) and neovascular AMD, though the underlying mechanisms remain elusive. Previously we reported elevated TNF mRNA and protein expression in RD. In this study, we investigate the role of TNF in RD-induced photoreceptor degeneration.
RD and subsequent photoreceptor degeneration was caused by subretinal injection of hyaluronaic 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 thickness 7 days after RD. To understand the role of TNF in photoreceptor degeneration, RD was performed in mice deficient in TNF or its receptors (TNFRI, TNFRII, TNFRI&II), or in wild-type mice using a functionally blocking antibody to TNF. CD11b+ cells in the outer plexiform layer and subretinal space were counted by IHC.
RD-induced photoreceptor degeneration was significantly suppressed with specific blockade of TNF (p=0.032), in mice deficient for TNF (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). Müller cell activation was unchanged in wild-type and TNF-/- mice. Recruitment of CD11b+ monocytes was significantly lower in the TNF-/- mice compared to WT (p=0.0016).
TNF plays a critical role in RD-induced photoreceptor degeneration. This pathway may become an important target in the prevention of photoreceptor degeneration.
This PDF is available to Subscribers Only