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Editors Selection IGR 12-1

Surgical Therapy: SPARC deficiency increased bleb survival

Comment by Peng Tee Khaw & Sumit Dhingra on:

27656 SPARC deficiency results in improved surgical survival in a novel mouse model of glaucoma filtration surgery, Seet LF; Su R; Barathi VA et al., PLoS ONE, 2010; 5: 9415

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Secreted protein, acidic and rich in cysteine (SPARC) is a glycoprotein that interacts with a range of extracellular matrix molecules and therefore has an effect on cellular proliferation, migration, differentiation and contraction. In the eye, its role has been demonstrated in corneal wound repair, proliferative vitreoretinopathy, macular degeneration, and pathogenesis of glaucoma and cataract.

Conjunctival scarring is the main cause of failure following glaucoma surgery. The use of antimetabolites to prevent such scarring has improved outcomes in some, but not all patients. Furthermore, the use of these antimetabolites is associated with many potentially, blinding side effects. More powerful, as well as safer modulators of conjunctival wound healing are needed.

In this study, Seet et al. (2026) described a new experimental mouse model to study glaucoma surgery. Using this model, they have demonstrated that mice deficient in SPARC had significantly increased bleb survival, with histology of these blebs showing reduced collagen, smaller diameter collagen fibrils, and looser subconjunctival tissue.

Mice deficient in SPARC had significantly increased bleb survival

They have also demonstrated the use of anterior segment optical coherence tomography (AS-OCT) imaging and confocal microscopy of the subconjunctival blebs in this model. Additionally, they have confirmed these results using SPARC deficient fibroblasts in cell culture models of components of the healing process.

This mouse model has the advantages of low cost and availability, compared to the widely accepted rabbit model of conjunctival scarring. However, further improvements to the model (for example, using a fixed size cannula to achieve a consistent sclerostomy size) and clinical validation (with the use of a positive control such as Mitomycin) is required. For the further development of these findings into a novel therapeutic strategy, a study demonstrating a beneficial effect from a SPARC specific inhibitor is needed. This study is important in that it shows how laboratory research can point the way to possible further targets for wound modulation. In the longer term the challenges include developing and delivering such an agent safely and at an adequate dose at the site of surgery.

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