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Editors Selection IGR 19-2
Basic Science: Do statins influence aqueous secretion?
Comment by Nils Loewen on:
56206 Pharmacological regulation of SPARC by lovastatin in human trabecular meshwork cells, Villarreal G; Chatterjee A; Oh SS et al., Investigative Ophthalmology and Visual Science, 2014; 55: 1657-1665
SPARC (Secreted Protein Acidic and Rich in Cysteine) is a micro-RNA is expressed in the trabecular meshwork that has been implicated in IOP regulation and primary open-angle glaucoma (POAG) pathogenesis. Previous work by Villarreal et al. demonstrated that SPARC was highly up-regulated following TGF-b2 treatment in human TM cultures.1 In their current study, the authors reported the effect of lovastatin on SPARC, TGF-b2 and KLF4 in primary human TM cell monolayer cultures. They demonstrated that lovastatin inhibits SPARC expression, while increasing KLF4 expression. While the authors measured both mRNA and protein expression levels, the results suggest a much more significant effect on protein expression levels as compared to mRNA expression levels, as acknowledged in the discussion. This may suggest a post-transcriptional regulatory mechanism, or perhaps regulation through microRNA.
Statins, a class of medications approved for lowering cholesterol, may have utility in the treatment of glaucoma
The clinical significance of these findings is that statins, a class of medications approved for lowering cholesterol, may have utility in the treatment of glaucoma. However, the suggested mechanism for lovastatin regulation of SPARC and the direct effect of SPARC on IOP are not complete. Despite widespread use, initiation of statins has not yet been noticed to have an effect on IOP or the course of glaucoma. The involvement of both KLF4 and TGF-b2 in the mechanism, and the stronger effect on protein expression levels as compared with mRNA suggest that there is more to this mechanism, perhaps two separate pathways that ultimately affect SPARC expression. This work provides further insight into the molecular pathways involved in IOP and outflow regulation at the level of the TM. However, the mechanisms by which IOP are regulated, and the role of SPARC (causative or merely correlated) remains to be seen. The new data in this study is intriguing and perhaps pathway analysis tools2 could be applied to better understand the context.
References
- Villarreal G Jr, Oh D-J, Kang MH, Rhee DJ. Coordinated regulation of extracellular matrix synthesis by the microRNA-29 family in the trabecular meshwork. Invest. Ophthalmol Vis Sci 2011;52:3391-3397.
- Khatri P, Sirota M, Butte AJ. Ten years of pathway analysis: current approaches and outstanding challenges. PLoS Comput Biol 2012; 8, e1002375.
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