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Year : 2014  |  Volume : 60  |  Issue : 3  |  Page : 237-238

Toll like receptors and acute retinal necrosis syndrome- evaluating the association

Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra; Institute of Life Sciences, Bhubaneswar, Odisha, India

Date of Web Publication14-Aug-2014

Correspondence Address:
Dr. S Pathak
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra; Institute of Life Sciences, Bhubaneswar, Odisha
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Source of Support: None, Conflict of Interest: None

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How to cite this article:
Pathak S. Toll like receptors and acute retinal necrosis syndrome- evaluating the association. J Postgrad Med 2014;60:237-8

How to cite this URL:
Pathak S. Toll like receptors and acute retinal necrosis syndrome- evaluating the association. J Postgrad Med [serial online] 2014 [cited 2023 Jun 2];60:237-8. Available from:

Acute retinal necrosis syndrome is a well-known, potentially devastating, necrotizing vaso-oclusive retinitis affecting both healthy and immunocompromised patients. [1],[2] It is caused by several members of the herpes virus family, including the herpes simplex virus (HSV)-1, HSV-2, and varicella zoster virus. [1],[2],[3],[4]

In this issue of the journal, Moses et al. [5] report the induction of Toll-like receptor 3 (TLR3), TLR4, and TLR9 in the retinal pigment epithelial (ARPE-19) cell line in response to HSV-1 and HSV-2 infection. However, they do not comment upon the possible ligands of these TLRs. Villalba et al. (2012) [6] have reported the induction of TLR2 and TLR4 by HSV-1 infection in primary astrocytic culture and linked the TLR expression to viral replication as well as induction of endogenous ligands such as serum amyloid A. It is therefore likely that a similar mechanism is involved in increased TLR3, TLR4, and TLR9 expression on retinal pigment epithelial cells and this needs to be investigated further.

TLRs play a key role in the induction of immune and inflammatory responses to pathogens. They recognize conserved products of microbial metabolism, such as LPS, peptidoglycan, dsRNA, etc., and alert the immune system to the entry of pathogens. Activation of TLRs induces the expression of pro-inflammatory cytokines and costimulatory molecules that are crucial to initiation of adaptive responses. TLR3, TLR4, and TLR9 are especially important in antiviral defense, as their engagement by viral products can trigger the production of interferon (IFN)-α, IFN-β, and IFN-λ, which are vital for antiviral immunity [7] Indeed, TLR3-dependent induction of these three cytokines is critical for primary immunity to HSV-1 in the central nervous system in children [6] Based on the evidence that TLR3 ligands have been shown to be protective against encephalitis in a mouse model, the authors in their article justifiably argue that TLRs may be responsible for the antiviral response in HSV infections. However, downstream consequences of TLR engagement in vivo remain to be clarified.

TLR-mediated responses may either be beneficial or detrimental in the immunoprivileged central nervous system, depending upon the strength and timing of the activating signal (van Noort and Bsibsi, 2009). [8] TLRs may play a similar role in the eye, another immunoprivileged site, and may in fact be involved in precipitation of acute retinitis. Recent reports suggest that besides the virus, T cells, macrophages, and cytokines are actively involved in HSV retinitis (Zheng and Atherton, 2005). [9] Pro-inflammatory cytokines produced in response to the infection-such as TNF-α and IFN-γ-would be especially important in this context. Indeed, TNF-α has been shown to participate in the pathology of HSV-1 retinitis. Local inhibition of TNF-α mRNA by intraocular TNF-α antisense-oligonucleotide injection has been shown to reduce ocular inflammatory bystander damage and to reduce incidence and severity of retinitis in the mouse model (Grajewski et al., 2012). [10] The report by Moses et al. should thus be an impetus for further research in the role TLRs in pathology versus protection in HSV-retinitis in particular and HSV-CNS infections in general.

 :: References Top

1.Atherton SS. Acute retinal necrosis: Insights into pathogenesis from the mouse model. Herpes 2001;8:69-73.  Back to cited text no. 1
2.Lewis ML, Culbertson WW, Post JD, Miller D, Kokame GT, Dix RD. Herpes simplex virus type 1. A cause of the acute retinal necrosis syndrome. Ophthalmology 1989;96:875-8.  Back to cited text no. 2
3.Thompson WS, Culbertson WW, Smiddy WE, Robertson JE, Rosenbaum JT. Acute retinal necrosis caused by reactivation of herpes simplex virus type 2. Am J Ophthalmol 1994;118:205-11.  Back to cited text no. 3
4.Hellinger WC, Bolling JP, Smith TF, Campbell RJ. Varicella-zoster virus retinitis in a patient with AIDS-related complex: Case report and brief review of the acute retinal necrosis syndrome. Clin Infect Dis 1993;16:208-12.  Back to cited text no. 4
5.Moses S, Jambulingam M, Madhavan HN. A pilot study on expression of toll like receptors (TLRs) in response to herpes simplex virus (HSV) infection in acute retinal pigment epithelial cells (ARPE) cells. J Postgrad Med 2014;60:243-7.  Back to cited text no. 5
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6.Villalba M, Hott M, Martin C, Aguila B, Valdivia S, Quezada C, et al. Herpes simplex virus type 1 induces simultaneous activation of Toll-like receptors 2 and 4 and expression of the endogenous ligand serum amyloid A in astrocytes. Med Microbiol Immunol 2012;201:371-9.   Back to cited text no. 6
7.Zhang SY, Jouanguy E, Sancho-Shimizu V, von Bernuth H, Yang K, Abel L, et al. Human toll-like receptor-dependent induction of interferons in protective immunity to viruses. Immunol Rev 2007;220:225-36.  Back to cited text no. 7
8.van Noort JM, Bsibsi M. Toll-like receptors in the CNS: Implications for neurodegeneration and repair. Prog Brain Res 2009;175:139-48.  Back to cited text no. 8
9.Zheng M, Atherton SS. Cytokine profiles and inflammatory cells during HSV-1-induced acute retinal necrosis. Invest Ophthalmol Vis Sci 2005;46:1356-63.  Back to cited text no. 9
10.Grajewski RS, Li J, Wasmuth S, Hennig M, Bauer D, Heiligenhaus A. Intravitreal treatment with antisense oligonucleotides targeting tumor necrosis factor-α in murine herpes simplex virus type 1 retinitis. Graefes Arch Clin Exp Ophthalmol 2012;250:231-8.  Back to cited text no. 10


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