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Editors Selection IGR 10-4
Trabecular meshwork: Calcification
Comment by Abbot Clark on:
19636 Presence of an established calcification marker in trabecular meshwork tissue of glaucoma donors, Xue W; Comes N; Borrás T, Investigative Ophthalmology and Visual Science, 2007; 48: 3184-3194
A recent report by Xue et al. (852) suggests that trabecular meshwork ™ tissue calcification may play an important role in glaucomatous damage to the aqueous outflow pathway. In a previous study (Xue et al. IOVS 2006; 47: 997-1007), the authors reported the involvement of a bone morphogenic protein (BMP2) in TM cell calcification, which was inhibited by matrix GLA protein (MGP). In the current study, the authors used TM tissues from perfusion cultured glaucoma and normal donor eyes as well as cultured human TM cells to evaluate the expression and activity of calcification markers alkaline phosphatase (ALP) and calcification inhibitor MGP. They report increased ALP activity and decreased expression of MGP in TM tissues from perfusion cultured glaucoma donor eyes compared to normal eyes. They also show increased ALP activity and increased alizarin red staining in DEX and TGF&beta-2 treated cultured human TM cells.
None of the numerous extensive morphological and ultrastructural studies of the glaucomatous TM tissues have shown any evidence of calcificationAlirzarin red is a histological stain that reacts with calcium in tissues and cells. When they knock-down MGP expression in TM cells using siRNA, ALP expression is increased, suggesting coordinate regulation of these two genes. This unique calcification hypothesis is a very interesting and warrants additional study. The authors indicate that ALP is a marker of tissue calcification because ALP plays an important role in the calcification of bone. However, there are a number of ALP genes that are widely expressed in normal ocular tissues, and ALP is a broad specificity phosphatase, so ALP is not a unique marker for calcification. Likewise, although BMPs play a role in the formation of bone and cartilage, they also are widely expressed and have a wide variety of additional activities not related to bone formation. For example, BMP4 and BMP7 inhibit TGF&beta-2 induction of extracellular matrix proteins in the TM (Wordinger et al. IOVS 2007; 48: 1191-1200; Fuchshofer et al. IOVS 2007; 48: 715-726). To date, none of the numerous extensive morphological and ultrastructural studies of the glaucomatous TM tissues have shown any evidence of calcification. We eagerly await direct evidence supporting this calcification hypothesis, such as increased alizarin red staining or X-ray dispersion elemental STEM analysis of glaucomatous TM tissues.
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