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Editors Selection IGR 11-3
Basic Science: In vitro Trabecular Meshwork Model
Comment by Nils Loewen & Yalong Dang on:
65875 Bioengineered glaucomatous 3D human trabecular meshwork as an in vitro disease model, Torrejon KY; Papke EL; Halman JR et al., Biotechnology and bioengineering, 2016; 113: 1357-1368
The trabecular meshwork (TM) is guarding the intake of the outflow system of the eye and traditionally thought of as the primary cause of increased outflow resistance in primary and secondary open angle glaucomas.1 Establishment of a TM-based, ex vivo model to study outflow and screen drugs has great clinical and experimental value. Based on their previous study,2 Torrejon et al. created a bioengineered 3D human TM model which showed behavior similar to human steroid induced glaucoma after several days of treatment with prednisolone acetate.3 The expression of myocilin, deposition of extracellular matrix protein, transcellular electrical resistance and cytokines increased, while the expression of MMPs, phagocytic activities of TM cells and outflow facility decreased when compared with untreated controls. To further validate this model, a ROCK inhibitor (Y27632) and an actin disruptor (Lat-B) were also used. This reversed the steroid effect suggesting that this bioengineered 3D TM model can be utilized as a platform to study the pathophysiology of steroid induced glaucoma.
approximately 50% of the outflow resistance is downstream of the TM and similar at different severity stages of glaucoma following ab interno trabeculectomy
Overall, this study is very interesting and will provide a much needed in vitro model to study the complex TM responses without the necessity of an in vivo or ex vivo model. It would be interesting to see if the behavior of this model remains similar when TM cells are nondividing to better reflect their normal in situ behavior.
While this model will help to investigate the TM, the pathogenesis of open-angle glaucoma is still incompletely understood. New evidence indicates that approximately 50% of the outflow resistance is downstream of the TM and similar at different severity stages of glaucoma following ab interno trabeculectomy.4 This resistance remains even after the destruction of valve-like structures of the collector openings5,6 and points towards an unidentified outflow resistance in the collector channels or other parts of the aqueous humor drainage system. Organotypical ex vivo models7,8 might remain the only simplification for now to avoid costly and complex in vivo studies.
References
- Clark AF, Wordinger RJ. The role of steroids in outflow resistance. Exp Eye Res 2009;88(4):752-759.
- Torrejon KY, Pu D, Bergkvist M, et al. Recreating a human trabecular meshwork outflow system on microfabricated porous structures. Biotechnol Bioeng 2013;110(12):3205-3218.
- Torrejon KY, Papke EL, Halman JR, et al. Bioengineered glaucomatous 3D human trabecular meshwork as an in vitro disease model. Biotechnol Bioeng 2016;113(6):1357-1368.
- Loewen RT, Roy P, Parikh HA, et al. Impact of a Glaucoma Severity Index on Results of Trabectome Surgery: Larger Pressure Reduction in More Severe Glaucoma. PLoS One 2016;11(3):e0151926.
- Pajic B, Pajic-Eggspuehler B, Haefliger I. New minimally invasive, deep sclerotomy ab interno surgical procedure for glaucoma, six years of follow-up. J Glaucoma 2011;20(2):109-114.
- Singh D, Bundela R, Agarwal A, Bist HK, Satsangi SK. Goniotomy ab interno 'a glaucoma filtering surgery' using the Fugo Plasma Blade. Ann Ophthalmol 2006;38(3):213-217.
- Loewen RT, Roy P, Park DB, et al. A Porcine Anterior Segment Perfusion and Transduction Model With Direct Visualization of the Trabecular Meshwork. Invest Ophthalmol Vis Sci 2016;57(3):1338-1344.
- Loewen RT, Brown EN, Scott G, Parikh H, Schuman JS, Loewen NA. Quantification of Focal Outflow Enhancement using Differential Canalograms. Invest Ophthalmol Vis Sci (in press) 2016:044503. doi:10.1167/iovs.16-19541.
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