Tank-binding kinase 1 regulates inflammation and autophagy in glaucoma

Area of Science:

• Ophthalmology
• Genetics
• Neuroscience

Background:

• Familial normal tension glaucoma (NTG) is linked to TANK-binding kinase (TBK1) copy number variations.
• Unlike primary open-angle glaucoma (POAG), NTG occurs without elevated intraocular pressure (IOP).
• Current glaucoma treatments focus on lowering IOP, necessitating alternative therapeutic strategies.

Purpose of the Study:

• To review the genetic and molecular roles of TBK1 in glaucomatous pathology.
• To consolidate current knowledge on TBK1's contribution to normal tension glaucoma (NTG).
• To identify research gaps and guide future therapeutic strategies targeting TBK1 pathways.

Main Methods:

• Literature review consolidating current knowledge on TBK1.
• Analysis of TBK1's genetic and molecular roles in glaucoma.
• Identification of research gaps in TBK1's contribution to NTG.

Main Results:

• TBK1 copy number variations are a monogenic cause of familial NTG.
• TBK1's roles in NF-κB, IRF signaling, and autophagy may contribute to RGC stress and ON damage.
• TBK1 influences glaucomatous neurodegeneration independent of IOP.

Conclusions:

• TBK1 plays a significant role in the pathogenesis of normal tension glaucoma (NTG).
• Understanding TBK1's molecular mechanisms is crucial for developing novel NTG therapies.
• Targeting TBK1 pathways offers a promising therapeutic avenue for glaucoma.