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

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 174 ◽  
Author(s):  
Yalong Dang ◽  
Susannah Waxman ◽  
Chao Wang ◽  
Priyal Shah ◽  
Ralitsa T. Loewen ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Trabecular Meshwork ◽  
Ex Vivo ◽  
Pigment Dispersion ◽  
Pigmentary Glaucoma ◽  
Fluorescent Microspheres ◽  
Phagocytic Capacity ◽  
Pressure Transducers ◽  
Intraocular Pressure Elevation ◽  
Iop Elevation

Background: Outflow regulation and phagocytosis are key functions of the 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. Methods: Sixteen porcine anterior chamber cultures received a continuous 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. Results: The baseline IOPs in Pg and C were similar (P=0.82). A significant IOP elevation occurred in Pg at 48, 120, and 180 hours (all P<0.01, compared 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). Conclusions: In this porcine model of pigmentary glaucoma, an IOP elevation occurs much earlier than when phagocytosis fails, suggesting that two separate mechanisms might be at work.

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

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 174
Author(s):  
Yalong Dang ◽  
Susannah Waxman ◽  
Chao Wang ◽  
Priyal Shah ◽  
Ralitsa T. Loewen ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Trabecular Meshwork ◽  
Ex Vivo ◽  
Pigment Dispersion ◽  
Pigmentary Glaucoma ◽  
Fluorescent Microspheres ◽  
Phagocytic Capacity ◽  
Pressure Transducers ◽  
Intraocular Pressure Elevation ◽  
Iop Elevation

Background: Outflow regulation and phagocytosis are key functions of the 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. Methods: Sixteen porcine anterior chamber cultures received a continuous 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. Results: The baseline IOPs in Pg and C were similar (P=0.82). A significant IOP elevation occurred in Pg at 48, 120, and 180 hours (all P<0.01, compared 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). Conclusions: In this porcine model of pigmentary glaucoma, an IOP elevation occurs much earlier than when phagocytosis fails, suggesting that two separate mechanisms might be at work.

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

2017 ◽  
Author(s):  
Yalong Dang ◽  
Susannah Waxman ◽  
Chao Wang ◽  
Ralitsa T. Loewen ◽  
Nils A. Loewen
Keyword(s):  
Intraocular Pressure ◽  
Trabecular Meshwork ◽  
Ex Vivo ◽  
Pigment Dispersion ◽  
Pigmentary Glaucoma ◽  
Ex Vivo Model ◽  
Phagocytic Capacity ◽  
Pressure Transducers ◽  
Intraocular Pressure Elevation ◽  
Iop Elevation

AbstractPurposeOutflow regulation and phagocytosis are key functions of the 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.Materials and MethodsSixteen porcine anterior chamber cultures received a continuous infusion of pigment granules (P), 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.ResultsThe baseline IOPs in P and C were similar (P=0.82). A significant IOP elevation occurred in P at 48, 120, and 180 hours (all P<0.01, compared 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).ConclusionIn this porcine model of pigmentary glaucoma, an IOP elevation occurs much earlier than when phagocytosis fails, suggesting that two separate mechanisms might be at work.

scholarly journals A porcine ex vivo model of pigmentary glaucoma

2017 ◽  
Author(s):  
Yalong Dang ◽  
Susannah Waxman ◽  
Chao Wang ◽  
Ralista T. Loewen ◽  
Ming Sun ◽  
...  
Keyword(s):  
Trabecular Meshwork ◽  
Ex Vivo ◽  
Pigment Dispersion ◽  
Pigmentary Glaucoma ◽  
Ex Vivo Model ◽  
Pigment Dispersion Syndrome ◽  
And Behavior ◽  
Human Eyes ◽  
Pigment Accumulation

AbstractPigment dispersion syndrome can lead to pigmentary glaucoma (PG), a poorly understood condition of younger, myopic eyes with fluctuating, high intraocular pressure (IOP). The absence of a model similar in size and behavior to human eyes has made it difficult to investigate its pathogenesis. Here, we present a porcine ex vivo model that recreates the features of PG including intraocular hypertension, pigment accumulation in the trabecular meshwork and relative failure of phagocytosis. Inin vitromonolayer cultures as well as inex vivoeye perfusion cultures, we found that the trabecular meshwork (TM) cells that regulate outflow, form actin stress fibers and have a decreased phagocytosis. Gene expression microarray and pathway analysis indicated key roles of RhoA in regulating the TM cytoskeleton, motility, and phagocytosis thereby providing new targets for PG therapy.

scholarly journals Ripasudil in a model of pigmentary glaucoma

2020 ◽  
Author(s):  
C Wang ◽  
Y Dang ◽  
S Waxman ◽  
Y Hong ◽  
P Shah ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
High Power ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Rho Kinase ◽  
Stress Fibers ◽  
Pigment Dispersion ◽  
Pigmentary Glaucoma ◽  
High Power Field

AbstractPurposeTo investigate the effects of Ripasudil (K-115), a Rho-kinase inhibitor, in a porcine model of pigmentary glaucoma.MethodsHallmark features of trabecular meshwork (TM), the principle structure of the outflow system affected in this model, were analyzed. In vitro TM cells and ex vivo perfused eyes were subjected to pigment dispersion followed by K-115 treatment (PK115). PK115 was compared to sham-treated controls (C) and pigment (P). Cytoskeletal alterations were assessed by F-actin labeling. TM cell phagocytosis of fluorescent targets was evaluated by flow cytometry. Cell migration was studied with a wound-healing assay. Intraocular pressure was continuously monitored and compared to after the establishment of the pigmentary glaucoma model and after treatment with K-115.ResultsIn vitro, the percentage of cells with stress fibers increased in response to pigment but declined sharply after treatment with K-115 (P: 32.8 +/- 2.9%; PK115: 11.6 +/- 3.3%, P < 0.001). Phagocytosis first declined but recovered after K-115 (P: 25.7+/-2.1%, PK115: 33.4+/-0.8%, P <0.01). Migration recuperated at 12h with K-115 treatment (P: 19.1+/-4.6 cells/high-power field, PK115: 42.5+/-1.6 cells/high-power field, P <0.001). Ex vivo, eyes became hypertensive from pigment dispersion but were normotensive after treatment with K-115 (P: 20.3 +/- 1.2 mmHg, PK115: 8.9 +/- 1.7 mmHg; P< 0.005).ConclusionIn vitro, K-115 reduced TM stress fibers, restored phagocytosis, and restored migration of TM cells. Ex vivo, K-115 normalized intraocular pressure.

scholarly journals A Porcine Ex Vivo Model of Pigmentary Glaucoma

2018 ◽  
Author(s):  
Yalong Dang ◽  
Susannah Waxman ◽  
Chao Wang ◽  
Ralitsa T. Loewen ◽  
Ming Sun ◽  
...  
Keyword(s):  
Trabecular Meshwork ◽  
Ex Vivo ◽  
Anterior Segment ◽  
Pigment Dispersion ◽  
Pigmentary Glaucoma ◽  
Ex Vivo Model ◽  
Trabecular Meshwork Cells ◽  
Gene Expression Microarrays ◽  
Expression Microarrays ◽  
And Behavior

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.

scholarly journals An Iconic Case of Pigmentary Glaucoma: Brief Review of the Literature

2020 ◽  
Vol 11 (2) ◽  
pp. 377-384
Author(s):  
Mariachiara Di Pippo ◽  
Chiara Ciancimino ◽  
Luca Scuderi ◽  
Andrea Perdicchi
Keyword(s):  
Intraocular Pressure ◽  
Trabecular Meshwork ◽  
Corneal Endothelium ◽  
Posterior Part ◽  
Pigment Dispersion ◽  
Pigmentary Glaucoma ◽  
Anterior Surface ◽  
Review Of The Literature ◽  
Pigment Dispersion Syndrome

Pigment dispersion syndrome and pigmentary glaucoma are two conditions characterized by pigment dispersion originating from the posterior part of the iris and its accumulation on the trabecular meshwork, corneal endothelium, and anterior surface of the lens. The pigment on the trabecular meshwork can cause chronic inflammation with a secondary reduction of its function and an increase in intraocular pressure. The case presented represents a typical example of pigmentary glaucoma in a myopic patient in which all the signs, symptoms, and complications typical of these pathologies were present. We report and describe an 8-year-long follow-up period with clinical and instrumental examinations.

scholarly journals A Case of Iris Melanocytoma Demonstrating Diffuse Melanocytic Proliferation with Uncontrolled Intraocular Pressure

2017 ◽  
Vol 8 (1) ◽  
pp. 190-194 ◽  
Author(s):  
Mami Kusunose ◽  
Yuji Sakino ◽  
Yoshihiro Noda ◽  
Tsutomu Daa ◽  
Toshiaki Kubota
Keyword(s):  
Electron Microscopy ◽  
Intraocular Pressure ◽  
Tumor Cells ◽  
Trabecular Meshwork ◽  
Light And Electron Microscopy ◽  
Secondary Glaucoma ◽  
Pigment Dispersion ◽  
Large Tumor ◽  
History Of ◽  
Ring Melanoma

We report a rare case with histologically proven melanocytoma of the iris that demonstrated diffuse melanocytic proliferation with uncontrolled secondary glaucoma and investigate the etiology of the intraocular pressure elevation. The patient was a 78-year-old man with a history of darkened iris of his left eye. The intraocular pressure was 39 mm Hg. A slit-lamp examination showed a diffuse darkened iris, and a gonioscopic examination revealed open angle with circumferential heavy pigmentation. There was no pigment dispersion of the anterior chamber and no pigment deposition of the cornea. We suspected malignant ring melanoma in the left eye and enucleated it. The globe was examined with light and electron microscopy. Light microscopy revealed the presence of heavily pigmented tumor cells in the iris, ciliary body, trabecular meshwork, and Schlemm’s canal. A bleached preparation showed large tumor cells with central and paracentral nuclei without mitosis. Electron microscopy of the trabecular meshwork revealed melanin-bearing tumor cells invading the intertrabecular spaces, and the melanin granules were not phagocytosed in the trabecular cells. The mechanical obstruction of the aqueous flow by the tumor cells may be a major cause of secondary glaucoma in eyes with iris melanocytoma presenting diffuse proliferation.

scholarly journals Impact of Pigment Dispersion on Trabecular Meshwork Cells

2018 ◽  
Author(s):  
Chao Wang ◽  
Yalong Dang ◽  
Ralitsa Loewen ◽  
Susannah Waxman ◽  
Priyal Shah ◽  
...  
Keyword(s):  
Trabecular Meshwork ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Signaling Cascades ◽  
Pigment Dispersion ◽  
Pigmentary Glaucoma ◽  
Trabecular Meshwork Cells ◽  
Stress Fiber Formation ◽  
Ab Interno Trabeculectomy ◽  
And Migration

Purpose: To investigate the effect of pigment dispersion on trabecular meshwork (TM) cells. Methods: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose, migrate, and contract were quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. Results: TM cells readily phagocytosed pigment granules. Pigment induced stress fiber formation (pigment (P): 60.1 &plusmn; 0.3%, n = 10, control (C): 38.4 &plusmn; 2.5%, n = 11, P &lt; 0.001) and contraction at 24 hours onward (P &lt; 0.01). Phagocytosis declined (P: 68.7 &plusmn; 1.3%, C: 37.0 &plusmn; 1.1%, n = 3, P &lt; 0.001) and migration was reduced after 6 hours (P: 28.0.1 &plusmn; 2.3, n = 12, C: 40.6 &plusmn; 3.3, n = 13, P &lt; 0.01). Microarray analysis revealed that Rho, IGF-1, and TGF&beta; signaling cascades were central to these responses. Conclusions: TM cell exposure to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigmentary glaucoma.

scholarly journals Changes in Vessel Density of the Patients with Narrow Antenior Chamber after an Acute Intraocular Pressure Elevation Observed by OCT Angiography

2019 ◽  
Author(s):  
ziwei Ma ◽  
WENHAN QIU ◽  
DANNI ZHOU ◽  
WEIHUA YANG ◽  
XUEFENG PAN ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Retinal Vessel ◽  
Vessel Density ◽  
Significant Difference ◽  
Intraocular Pressure Elevation ◽  
Acute Elevation ◽  
Group A ◽  
Prospective Comparative Study ◽  
Iop Elevation ◽  
Group B

Abstract Background:Although the pathogenesis of glaucoma is not fully understood ,an elevated intraocular pressure (IOP) is a major factor contributing to its development and progression. The aim of this study was to investigate the changes in the vessel densities of the macula and optic nerve head (ONH) after an acute elevation in the intraocular pressure (IOP) observed using optical coherence tomography angiography (OCTA). Methods: This was a prospective comparative study of subjects with narrow anterior chamber angles who underwent laser peripheral iridotomies (LPIs). The IOP was measured before and one hour after the LPI. The retinal vessel densities of the macula and ONH were measured using OCTA at the baseline and one hour after the LPI. Results: A total of 64 eyes of 51 individuals were enrolled in this study, and 58 eyes of 43 individuals finally completed the study with a mean IOP rise of 10.5 ± 7.6 mmHg after the LPI. Based on the magnitude of the rise in the IOP, we divided the subjects into three groups: group A = IOP rise ≤ 10 mmHg, group B = 10 mmHg < IOP rise ≤ 20 mmHg, and group C = IOP rise > 20 mmHg. The vessel density did not differ after the acute IOP elevation in either the macular region or papillary region in group A or group B (p > 0.05), but there was a significant difference in group C (p < 0.05). However, when the subjects were not separated into groups, the vessel densities of the ONH and macular region did not differ between the measurements obtained at the baseline and one hour after the LPI (p>0.05). The correlation existed in peripapillary and macular vessel density (p < 0.05). Conclusion: In these subjects with narrow antenior chamber, an acute mild or moderate IOP elevation for one hour after the LPI did not affect the vessel density in the macula or ONH, as examined using OCTA. However, when the IOP rise was greater than 20 mmHg, the macular and papillary vessel density decreased significantly.

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