Date of Award

2013

Document type

Thesis

Degree Name

MSc by research (Master of Science by research)

First Supervisor

Dr Caroline Jeffries

Second Supervisor

Professor Conor C Murphy

Funder/Sponsor

Pfize; Irish College of Ophthalmologists

Keywords

Keratitis, Herpetic

Abstract

Herpes Simples Keratitis (HSK) is the commonest cause of infectious blindness in the developed world. It is caused by HSV-l which is a large double stranded DNA virus which can invade the cornea and after treatment remains latent in the trigeminal ganglia. Toll like receptors are key components of the innate immune system and are highly expressed in the corneal epithelium. HSV-l induces upregulation of several Toll Like Receptors (TLRs) and triggers the release of anti-viral cytokines. In certain cases HSV-l has evolved to avoid these innate anti-viral responses and can cause lifelong recurrent infection. This recurrent keratitis causes lesions which are immunoinflammatory in nature, can recur throughout life and cause progressive corneal scarring, vascularisation, thinning and may require a corneal transplant which does not have a good long-term outcome. Understanding the mechanisms that cause this disease may lead to improved or novel therapies that will help the long-term outcome of HSK patients. This study aims to examine the immune responses of HSK patient peripheral blood mononuclear cells (PBMC) before and after treatment compared to healthy donors. Our work has shown that peripheral blood mononuclear cells (PBMCs) show differences in their ability to respond to various TLR ligands both in relation to the cytokines they produce and upregulation of cell surface markers. In particular our results show that IL-1(3, a key proinflammatory cytokine is elevated in serum of active patients compared to inactive patients, thus demonstrating that peripheral immune responses are activated in response to HSV infection of the cornea. In addition our work has shown that although active patients expressed activation markers on T cells and B cells but differences were inconclusive based on patient numbers (active/inactive n=5, control n=4). Further data indicated that the TLR 3 pathway is compromised in active patient PBMCs, potentially having implications for HSV-l viral clearance and viral replication and HSK persists in the cornea.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

File Size

3.8MB

Comments

This thesis is submitted to the Royal College of Surgeons in Ireland for the Degree of Master of Science (MSc).

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