The structure of the trabecular meshwork, its connections to the ciliary muscle, and the effect of pilocarpine on outflow facility in mice.
OBJECTIVE
To determine the connections between the ciliary muscle (CM), trabecular meshwork (TM), and Schlemm's canal (SC) and their innervations that allows CM contraction (by pilocarpine) to influence conventional outflow in mice.


METHODS
Sequential sections and whole mounts of murine corneoscleral angles were stained for elastin, α-smooth muscle actin (αSMA), vesicular acetylcholine transporter (VAChT), neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), and tyrosine hydroxylase (TH). Elastic (EL) fibers between the CM, TM, and SC were examined in ultrathin, sequential sections from different planes. The effect of pilocarpine (100 μM) on conventional outflow facility was measured by perfusion of enucleated mouse eyes.


RESULTS
The mouse TM contains a three-dimensional (3D) net of EL fibers connecting the inner wall of SC to the cornea anteriorly, the ciliary body (CB) internally and the choroid and CM posteriorly. The CM bifurcates near the posterior TM, extending outer tendons to the juxtacanalicular tissue and inner wall of SC and internal connections to the lamellated TM and CB. Ciliary muscle and lamellated TM cells stain with αSMA and are innervated by VAChT-containing nerve fibers, without TH, VIP, or nNOS. Pilocarpine doubled outflow facility.


CONCLUSIONS
Mouse eyes resemble primate eyes not only by their well developed SC and TM, but also by their 3D EL net tethering together the TM and SC inner wall and by the tendinous insertion of the CM into this net. The increase in outflow facility following cholinergic stimulation in mice, as in primates, supports using mice for studies of aqueous humor dynamics and glaucoma.
Department of Bioengineering, Imperial College London, London, United Kingdom.
Darryl R
DR
Overby
Department of Bioengineering, Imperial College London, London, United Kingdom.
Jacques
J
Bertrand
Department of Anatomy II, University of Erlangen-Nürnberg, Germany.
Martin
M
Schicht
Department of Anatomy II, University of Erlangen-Nürnberg, Germany.
Friedrich
F
Paulsen
Department of Ophthalmology, Duke University, Durham, North Carolina, United States.
W Daniel
WD
Stamer
Department of Anatomy II, University of Erlangen-Nürnberg, Germany.
Elke
E
Lütjen-Drecoll
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002924:Ciliary Body / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure*; D004195:Disease Models, Animal; D005901:Glaucoma / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D018721:Muscarinic Agonists / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology*; D014129:Trabecular Meshwork / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure*
D018721:Muscarinic Agonists; D010862:Pilocarpine
aqueous humor; ciliary muscle; glaucoma; pilocarpine; trabecular meshwork