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Editors Selection IGR 11-2

Surgical Treatment: Molteno implant and extracellular matrix turnover

Comment by Richard Lee on:

23947 Otago Glaucoma Surgery Outcome Study: the pattern of expression of MMPs and TIMPs in bleb capsules surrounding Molteno implants, McCluskey P; Molteno A; Wakefield D et al., Investigative Ophthalmology and Visual Science, 2009; 50: 2161-2164

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McCluskey et al. (893) present immuno histochemical evidence that Molteno glaucoma drainage implant (GDI) blebs preferentially express certain matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). Ten eyes with Molteno implants placed for two months to almost 23 years secondary to various types of glaucoma (i.e., pseudoexfoliation, primary open angle, trauma, ghost cell, and neovascular) were studied relative to the expression of MMP-1, -2, and -3 and TIMP-1, -2, and -3.

The blebs expressed mainly TIMP-2 and little or no TIMP-1 or TIMP-3, depending on the eye. TIMP-2 appeared to be expressed mainly within the inner fibrodegenerative layer near the bleb wall, suggesting not only a preference for TIMP-2 expression but also a spatial localization within the three layers of the bleb wall (as described by Molteno). MMP-1 was the most intensively staining, whereas MMP-2 and MMP-3 immunostained less intensely based upon a qualitative assessment.

Collagen and extracellular matrix turnover is dynamic and affects glaucoma drainage implant function

This study suggests the intriguing idea that collagen and extracellular matrix turnover is dynamic and affects GDI function. However, this suggestion has to be tempered by the fact that MMPs and TIMPs interact dynamically and that the presence of an MMP or TIMP in a particular location does mean it is active, since MMPS may be inactive secondary to binding TIMPs. The authors would have benefited from double and triple staining to see if TIMPs and MMPs co-localized, suggesting bound inactive proteinases. In addition, the MMPs are part of a large and growing family of over 20 members ‐ any of which could also be expressed and enzymatically active in GDI blebs. Lastly, as the authors point out, regulators of MMPs and TIMPs are present in aqueous humor circulating through the blebs ‐ these molecules would not have been detected by the immunostaining of the bleb tissue. Ideally, the aqueous humor and bleb capsular tissues would have been proteomically analyzed for the presence of all TIMPS and MMPs. In this paper, the authors suggest the intriguing possibility that extracellular matrix turnover may regulate GDI bleb function. This concept could lead to the development of treatments that could alter GDI bleb structure and improve bleb function.
This study suggests the intriguing idea that collagen and extracellular matrix turnover is dynamic and affects GDI function.

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