**Abbreviations**

these different functions of optineurin is not clear. Since optineurin is an adaptor protein, mutations in it can lead to altered interactions with other proteins impairing its normal cellular functions. Identifying the functions that are affected by disease-associated mutations of optineurin is a major challenge towards understanding the molecular mechanisms of etiopa‐ thogenesis of neurodegenerative disease like glaucoma. Presently, our understanding of the molecular mechanisms of functional defects caused by E50K mutation, the best studied mutant, is far from complete. Several questions remain to be answered. How does E50K mutation cause a block in autophagy? Does E50K mutant cause inhibition of secretion of neutrophins/survival factors? Is Rab8 involved in this process? Does impaired transferrin receptor trafficking or function contribute to E50K-induced RGC death? How does H486R mutant cause glaucoma? Does it cause autoimmune defects by impairing the function of CYLD? How do other mutants of optineurin alter its function? Why some mutations cause ALS and others cause glaucoma? Are mutations of optineurin also prevalent in other neuro‐ degenerative diseases? Is interaction of optineurin or its mutants altered with huntingtin or its mutants? If so, what is its relevance for Huntington's disease and glaucoma? Role of various mutants of optineurin in affecting known functions of optineurin needs to be examined. This would help in understanding the molecular mechanisms of pathogenesis of glaucoma and other neurodegenerative diseases. Most of the optineurin mutants do not directly induce death of RGC-5 cells upon overexpression, indicating, therefore, that these optineurin mutations might cause glaucoma by indirect mechanisms involving defects in other cells/tissues (Figure 6]. Survival of RGCs is influenced by other accessory cells like glial cells. Role of optineurin

118 Glaucoma - Basic and Clinical Aspects

mutants in autoimmunity and glial cell activation needs to be explored.

**Figure 6.** Overview of role of optineurin mutations in causing Glaucoma.

RGC, Retinal ganglion cells; IOP, Intraocular pressure; POAG, Primary open angle glaucoma; JOAG, Juvenile open angle glaucoma; NTG, Normal tension glaucoma; ACG, Angle closure glaucoma; TIGR, trabecular meshwork inducible glucocorticoid response; WDR36, WD repeat 36; CYP1B1, cytochrome p4501B1; NTF3/4, neurotrophin3/4; ALS, amyotrophic lateral sclerosis; UBD, ubiquitin-binding domain; GLUT4, glucose transporter member 4; EGF, epidermal growth factor; GAP, GTPase activating protein; NF-κB, Nuclear factor κB; IκB, inhibitor of kB; TNFα, tumor necrosis factor α; TNFR1, tumor necrosis factor Receptor1; TRADD- TNFR1-associated DEATH domain protein; TRAF2, TNF receptor associated factor 2; RIP, receptor interacting protein; IKK, IκB kinase; NEMO, NF-κB essential modifier; UXT, ubiquitously-expressed transcript; LC3- microtubule-associated protein 1 light chain 3; CTNF, ciliary neurotrophic factor; Plk1, Polo-like kinase; MYPT1, myosin phosphatase target subunit 1; Cdk1, cyclin dependent kinase 1; IRF3, Interferon regulatory factor 3; TBK1, TANK binding kinase; MDA5, melanoma differentiation associated gene 5; TRIF, TIR-domain-containing adapter-inducing interferon-β; ROS, reactive oxygen species; RIG1, retinoic acid inducible gene 1.
