Histologic Findings in Pigment Dispersion Syndrome and Pigmentary Glaucoma

Gottanka, Johannes; Johnson, Douglas H.; Grehn, Franz; Lütjen–Drecoll, Elke

doi:10.1097/00061198-200604000-00011

Cited by 67 publications

(63 citation statements)

References 26 publications

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“…Genes for cell motility were significantly upregulated, possibly reflecting migration of TM cells into Schlemm's canal, as has been reported in human PG 9,27 . We observed a decline in cell-matrix adhesions and an altered cytoskeleton, as reported in another study 67 .…”

Section: Discussionsupporting

confidence: 69%

“…We developed a porcine eye model of PG that replicates clinical features including pigment granules in the aqueous humor 8 and inside of TM cells 9,27,28 .…”

Section: Resultsmentioning

confidence: 99%

“…This may explain why the pathology of TM in PG is so different from that in pigment dispersion syndrome 28 . Gottanka et al 9 found that the Schlemm's canal in human PG specimens was partially (25%-65%) obstructed by loosely arranged, distended juxtacanalicular TM cells.…”

Section: Discussionmentioning

confidence: 99%

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A Porcine Ex Vivo Model of Pigmentary Glaucoma

Dang¹,

Waxman²,

Wang³

et al. 2018

Preprint

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Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.

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Section: Discussionsupporting

confidence: 69%

“…We developed a porcine eye model of PG that replicates clinical features including pigment granules in the aqueous humor 8 and inside of TM cells 9,27,28 .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

A Porcine Ex Vivo Model of Pigmentary Glaucoma

Dang¹,

Waxman²,

Wang³

et al. 2018

Preprint

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“…Pigment treatment has previously been shown to cause ocular hypertension in part by reorganizing the TM actin cytoskeleton and not by physical obstruction of the outflow tract 7,21 . We have recently reported that long, thick, and continuous TM actin bundles emerge as early as 24 hours after pigment exposure 3 and replicate this observation in the present study.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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.

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“…TM cells are gradually lost throughout life in all individuals and, under normal circumstances, they are not replaced (15). A number of studies have demonstrated that loss of TM cells is higher in POAG patients than in age-matched controls (16)(17)(18). The effects of lower TM cellularity are currently unclear, but it has been proposed that reduced TM cellularity, or the functional decline of surviving TM cells, engenders a reduced ability to maintain TM homeostasis and causes structural aberrations within the TM.…”

mentioning

confidence: 99%

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

Zhu

Gramlich

Laboissonniere

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

133

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Glaucoma is a common cause of vision loss or blindness and reduction of intraocular pressure (IOP) has been proven beneficial in a large fraction of glaucoma patients. The IOP is maintained by the trabecular meshwork (TM) and the elevation of IOP in open-angle glaucoma is associated with dysfunction and loss of the postmitotic cells residing within this tissue. To determine if IOP control can be maintained by replacing lost TM cells, we transplanted TM-like cells derived from induced pluripotent stem cells into the anterior chamber of a transgenic mouse model of glaucoma. Transplantation led to significantly reduced IOP and improved aqueous humor outflow facility, which was sustained for at least 9 wk. The ability to maintain normal IOP engendered survival of retinal ganglion cells, whose loss is ultimately the cause for reduced vision in glaucoma. In vivo and in vitro analyses demonstrated higher TM cellularity in treated mice compared with littermate controls and indicated that this increase is primarily because of a proliferative response of endogenous TM cells. Thus, our study provides in vivo demonstration that regeneration of the glaucomatous TM is possible and points toward novel approaches in the treatment of this disease.G laucoma is one of the most common causes of irreversible vision loss and blindness worldwide; ∼60 million suffer from this disease, and of these, 7 million are blind (1). By definition all glaucoma involves some degree of vision loss, which is because of the death of retinal ganglion cells (RGC), as well as degeneration of the optic nerve head, the optic nerve, and the lateral geniculate nucleus (2, 3). Advanced age and elevated intraocular pressure (IOP) are the two most significant risk factors for the development of glaucoma. Elevated IOP is typically a result of disturbances in the balance of aqueous humor production and drainage. Aqueous humor is continuously synthesized within the eye and drained primarily through the trabecular meshwork (TM), a specialized structure located anterior to the root of the iris. Although occlusion of the aqueous humor outflow pathways can occur through several mechanisms, in the United States and other Western populations the most common form of glaucoma is primary open angle glaucoma (POAG), which manifests no gross abnormalities to the anterior portion of the eye.Randomized clinical trials have shown that reduction of IOP slows the onset and progression of glaucoma, even in patients without suspicious elevation of IOP (4, 5). Although there has been increasing awareness that factors other than elevated IOP contribute to glaucomatous damage, to date all treatments for glaucoma remain aimed at reducing IOP either through surgical or medical means, which has resulted in significant preservation of vision and increased quality of life for millions of glaucoma patients (6, 7).Although the TM in eyes with POAG appears relatively normal at a gross morphological level, a number of more subtle changes influencing the mechanical properties of the TM collage...

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Histologic Findings in Pigment Dispersion Syndrome and Pigmentary Glaucoma

Cited by 67 publications

References 26 publications

A Porcine Ex Vivo Model of Pigmentary Glaucoma

A Porcine Ex Vivo Model of Pigmentary Glaucoma

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

Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo

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