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Invited Talks25Invited talks, Session VII, Glaucoma, August 1, 2010, 14.30 -16.00 hrsChairs: Kunal Ray and G Chandra SekharIIT 015Functional Defects Caused by Glaucoma-Associated Mutations of OptineurinGhanshyam SwarupCentre for Cellular & Molecular Biology, Hyderabad, India.Optineurin is a multifunctional protein involved in several functions such as vesicular traffickingfrom the Golgi to the plasma membrane and NF-kB regulation. Mutations in optineurin areassociated with glaucoma, a neurodegenerative eye disease that causes blindness. Geneticevidence suggests that the E50K (Glu50Lys) and H486R (His486Arg) are dominant diseasecausingmutations of optineurin. However, functional alterations caused by these mutations arenot known. We examined the role of optineurin and its mutants in endocytic recycling and NFkBregulation. Overexpression of the E50K mutant selectively induced death of retinal ganglioncells which was mediated by oxidative stress (IOVS, 2007). The E50K mutant causes defectiveendocytic recycling of transferrin receptor as shown by enlarged recycling endosomes, slowerdynamics of E50K vesicles and decreased transferrin uptake by the E50K-expressing cells. Ourresults suggest that optineurin regulates endocytic trafficking of transferrin receptor to therecycling endosomes. The E50K mutant impairs trafficking at the recycling endosomes due toaltered interactions with Rab8 and transferrin receptor (BMC Cell Biol. 2010). These resultshave implications for the pathogenesis of glaucoma caused by the E50K mutation becauseendocytic recycling is vital for maintaining homeostasis. We identified several novel optineurininteractingproteins, some of which are involved in signal transduction to the transcriptionfactor NF-kB (Ophthalmic Res. 2009). Optineurin negatively regulates TNFa-induced NF-kBactivation. Our results provide an insight into the mechanism of regulation of basal as wellas TNFa-induced NF-kB activity by optineurin. The H486R mutant is defective in regulatingNF-kB activation due to impaired interaction with a signaling protein.IIT 016Population Based Studies: Implications for Glaucoma Care in IndiaRonnie GeorgeSankara Nethralaya, Chennai, India.A number of population based studies on glaucoma have been conducted in India from acrossthe country in the past two decades. Together they provide important insights into theprevalence and incidence of glaucoma in the country. There is a substantial burden of primaryglaucoma with an additional risk of secondary disease and those at risk of glaucoma. Mostglaucoma in India is still undiagnosed. Risk factors reported in different studies show variations.These findings have implications for glaucoma management in the country. We will report whatthese findings mean for the ophthalmic practitioner and how they could be applied in the clinicin order to improve glaucoma detection and management.