Ahad, MA; (2013) Genetics of chemokines & cytokines in non-infectious posterior segment uveitis. Doctoral thesis (PhD), UCL (University College London).

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Abstract

Background and Aims: Non-infectious posterior segment uveitis is a potentially blinding disease that usually affects people of working age group. Like other immune mediated diseases, uveitis is a complex polygenic disease. Several cytokines have been identified as important regulators of the immune system during, induction, progression and remission of ocular inflammation in uveitis. The work described in this thesis is based on the hypothesis that polymorphisms in chemokine and cytokine genes can predict clinical outcome in non-infectious uveitis. Methods: Functional polymorphisms in sixteen chemokine and cytokine genes were genotyped and there associations were studied in a cohort of British Caucasians suffering with non-infectious posterior segment uveitis. Results: This study has shown that polymorphisms in IL-18, IL-10 & CCR2 genes can influence the susceptibility to certain phenotypes of non-infectious uveitis. Polymorphisms in many genes particularly, IL-1 , IL-6, CCR5 & IL-18 are found to affect the visual outcome and severity of the disease. Conclusion: The identification of these genetic variants that add susceptibility or resistance to uveitis has provided us further insights into the pathogenesis of uveitis. This work will help us identify patients who are at a greater risk of losing sight with this disease. This, in turn would allow tailored aggressive therapy to be given at presentation when vision is still good with a precise aim to prevent significant amount of blindness.

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