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Editors Selection IGR 10-4

Basic Research: TLR4 polymorphism in NTG

Comment by Khang Zhang on:

22243 Association of Toll-like receptor 4 gene polymorphisms with normal-tension glaucoma, Shibuya E; Meguro A; Ota M et al., Investigative Ophthalmology and Visual Science, 2008; 49: 4453-4457

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Shibuya et al. (1524) investigated whether TLR4 polymorphisms are associated with normal tension glaucoma (NTG). This was a casecontrol association study design, which recruited 250 patients with NTG and 318 healthy control subjects. Apparently, the authors wisely selected Japanese as subjects because Japanese has a relatively high prevalence of NTG comparing to other ethnicity. Strong linkage disequilibrium was observed among all eight single-nucleotide polymorphisms SNPs in the TLR4 gene, which were located in one haplotype block.

The immune system may have an important role in the development of NTG

The authors concluded that multiple SNPs in the TLR4 gene are associated with the risk of NTG and hypothesized ligands and/or cytokines involved in the TLR4 signaling network may be risk factors for the development of NTG. The result is very interesting. It implicates the immune-system as having an important role in the development of NTG. Since normal tension glaucoma, with insidious and asymptomatic onset, can be easily under-diagnosed and usually leads to severe consequences, this study helps to understand the etiology and pathology of NTG and provides potential important clues for treatment. However, this study doesn't include any data on function of TLR4. An explanation and discussion on the role of TLR4 and related molecules can be further strengthened by functional study. The complex network of immune system involved in development of NTG needs to be studied in details. Lastly, it is paramount that the same association study be replicated in multiple, independent cohorts.

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