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Editors Selection IGR 21-2

Experimental Glaucoma: An artificial trabecular meshwork for glaucoma research

Comment by Alex Huang on:

53928 Recreating a human trabecular meshwork outflow system on microfabricated porous structures, Torrejon KY; Pu D; Bergkvist M et al., Biotechnology and bioengineering, 2013; 110: 3205-3218

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Torrejon et al. tackle bioengineering a human in-vitro trabecular meshwork (TM) based on cell culture upon SU-8 scaffolds. SU-8 is an epoxy-based photoresist. Photoresist materials are light sensitive and can be modified by light. This photo-defining characteristic allows for creation of customizable porous scaffolds. After optimizing human TM cell culture conditions based on coat material, pore size, cell density, and culture time, the authors characterize their in-vitro TM along known in vivo characteristics. Cells take spindle shapes with nuclei and actin cytoskeleton arranged in an organized alignment. Cells grow multilayered giving some three-dimensionality (3D). Cells express proteins found in vivo in the TM (α-smooth muscle actin, myocilin, and αβ-crystallin) and in the extracellular matrix (collagen-IV and fibronectin). In a perfusion flow system, the in-vitro TM establishes a measurable outflow resistance and transmembrane pressure both of which are diminished by latruncunlin-B mediated cytoskeletal changes.

While a well-done and important step, a truly complete bio-engineered in-vitro conventional outflow model also contains additional compli- cated aspects. The authors acknowledge the absence of Schlemm's canal and its inner wall. While multi-layered, the 3D characteristic here resembles more the juxtacanalicular TM. Elements for full conventional outflow such as potential post-TM sources of resistance in the distal intra-scleral outflow pathway or innervation contributing a self-regulating aspect to the in-vivo TM are missing. In conclusion, this human in-vitro TM is a welcome step towards advancing TM biology to aid in the search for more outflow-targeted agents for intraocular pressure lowering in glaucoma. This system can serve as a platform for high-throughput drug or gene transfer screening. The advantages of such a system are great in the face of declining availability of fresh human tissue for research.

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