Intraocular pressure elevation precedes a phagocytosis decline in a model of pigmentary glaucoma

Abstract

Outflow regulation and phagocytosis are key functions of the Background: trabecular meshwork (TM), but it is not clear how the two are related in secondary open angle glaucomas characterized by an increased particle load. We hypothesized that diminished TM phagocytosis is not the primary cause of early ocular hypertension and recreated pigment dispersion in a porcine ex vivo model.Sixteen porcine anterior chamber cultures received a continuous Methods: infusion of pigment granules (Pg), while 16 additional anterior chambers served as controls (C). Pressure transducers recorded the intraocular pressure (IOP). The phagocytic capacity of the trabecular meshwork was determined by fluorescent microspheres.The baseline IOPs in Pg and C were similar ( =0.82). A significant Results: P IOP elevation occurred in Pg at 48, 120, and 180 hours (all <0.01, compared P to baseline). The pigment did not cause a reduction in TM phagocytosis at 48 hours, when the earliest IOP elevation occurred, but at 120 hours onward (P =0.001 compared to C). This reduction did not result in an additional IOP increase at 120 or 180 hours compared to the first IOP elevation at 48 hours (P >0.05).In this porcine model of pigmentary glaucoma, an IOP elevation Conclusions: occurs much earlier than when phagocytosis fails, suggesting that two separate mechanisms might be at work.

Structure-Function Changes of the Distal Outflow Tract in Response to Nitric Oxide

“…Consistent with our prior experience, 21,23,24,34,41,42 the perfused porcine anterior segments did not experience the amount of corneal edema reported with other culture techniques. 43 With intact TM, nitric oxide increased the facility by approximately 45% in group NO compared to the control group, C. After 360° AIT in experiment 2, we found a facility difference of approximately 60% between AIT-NO and AIT-C, in line with the findings reported by McDonnell et al 37 This difference persisted throughout experiments 1 and 2 but declined toward the end of experiment 1, possibly due to a decreasing TM facility response to NO.…”

“…The TM makes for a significant contribution to outflow resistance, but not in experiment 2 where the facility enhancement is TM-independent. Trabectome-mediated TM ablation results in an approximately 300 micron-wide excision down to the bare sclera 24,[31][32][33][34]41,44 where the opening of the collector channels are located without significant trauma or thermal injury. Like DETA-NO, cromakalim treatment of mouse eyes lowered episcleral venous pressures, and in TM-free human anterior segment cultures, lowered IOP.…”

Intraocular Pressure Reduction in a Pigmentary Glaucoma Model by Goniotome Ab Interno Trabeculectomy

“…The normal TM was lightly-pigmented ( Figure 4A). As seen before, 5,7 pigment granules were apparent in the TM at a density far below the amount expected to cause a physical obstruction after perfusion with pigment-supplemented media for 48 hours. The pigment granules were seen throughout the TM ( Figure 4B, yellow arrows).…”

“…5,6 Ocular hypertension emerges as soon as cytoskeletal changes occur and before phagocytosis declines. 7 Trabecular ablation, for instance, in Trabectome surgery (Neomedix Corp., Tustin, California, United States), can be effective in a range of glaucoma disease stages [8][9][10][11][12][13] which makes it well suited for PG. Ab interno angle surgeries rely on maintaining the anterior chamber either passively with a viscoelastic device 14,15 or actively, using an irrigation and aspiration (I&A) system.…”

“…19 In the present study, we hypothesized that trabecular excision with an I&A-equipped dual-blade device could also restore outflow by removing the pathology. We have extensive experience studying outflow in experimental systems, 20,21 including gene transfer, [22][23][24][25][26][27][28] disease modeling 5,7,19 and surgical outflow enhancement, 14,15,18,[29][30][31][32] but this is the first study of a microsurgical intervention for glaucoma in an ex vivo model of glaucoma.…”