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Editors Selection IGR 13-3

Basic Science: Trabecular structure and pilocarpine effects

Comment by Michael Fautsch on:

57211 The structure of the trabecular meshwork, its connections to the ciliary muscle, and the effect of pilocarpine on outflow facility in mice, Overby DR; Bertrand J; Schicht M et al., Investigative Ophthalmology and Visual Science, 2014; 55: 3727-3736

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One of the challenges in glaucoma research is the inability to generate animal models that represent the disease

One of the challenges in glaucoma research is the inability to generate animal models that represent the disease. This is in part due to the differences in outflow pathways between primate and non-primate animals. Mice, like humans, have a continuous Schlemm's canal, a lamellated trabecular meshwork and they do not exhibit washout. In this interesting study by Overby and colleagues, they describe the three-dimensional structure of the ciliary muscle in mice and found significant similarities with primate eyes. For example, the investigators found an intricate elastin fiber network that connects the inner wall of Schlemm's canal to the cornea anteriorly, the ciliary body internally and the choroid and ciliary muscle posteriorly. Additionally, the authors identified tendons extending from the ciliary muscle to the juxtacanalicular region, inner wall of Schlemm's canal and ciliary body, populating the extensive elastin network, similar to primate eyes. The authors also showed that the ciliary body and trabecular meshwork are innervated by VAChTcontaining nerve fibers, and that addition of pilocarpine can influence outflow facility in perfused eyes. Together, these findings show significant similarity to primate eyes suggesting that ciliary muscle tendon integration into the elastin network within the trabecular meshwork may provide a mechanism for active regulation of outflow by contraction and relaxation of the ciliary muscle. This would presumably affect outflow facility by maintaining patency of the Schlemm's canal by modulating tension on the inner wall and juxtacanalicular tissue, similar to what has been proposed for primates. This is an excellent paper that further validates mice as an animal model that can be used to understand the role of aqueous humor dynamics and IOP in normal and glaucoma-like models of the disease. Future studies examining aged mouse models will be important to determine whether they show thickening and extracellular matrix changes seen in human aged normal and glaucoma eyes.

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