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 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 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 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 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 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 Pigment dispersion syndrome with possible visual field loss (in Norwegian)

2010 ◽  
Vol 3 (1) ◽  
pp. 8-14
Author(s):  
Ellen Svarverud
Keyword(s):  
Trabecular Meshwork ◽  
Visual Fields ◽  
Anterior Segment ◽  
Clinical Signs ◽  
Visual Field Loss ◽  
Diagnostic Methods ◽  
Pigment Dispersion ◽  
Pigmentary Glaucoma ◽  
Pigment Dispersion Syndrome ◽  
Pigment Deposition

Pigment dispersion syndrome (PDS) is a condition of the anterior segment of the eye characterised by pigment deposition on a number of ocular structures. The condition is usually bilateral but most commonly asymmetric. In PDS, pigment is released from the posterior surface of the iris due to friction between the zonules and the iris. In itself, the condition does not represent any problems for the patient, but pigment deposition in the trabecular meshwork may interfere with drainage of the anterior chamber fluid and cause pigmentary glaucoma (PG). This case report presents a young myopic female with many of the classic signs of PDS; Krukenberg’s spindle, transillumination of mid-peripheral iris, deep anterior chambers, concave iris profile and increased pigmentation in the trabecular meshwork. Various diagnostic methods were applied to reveal clinical signs and to establish the patient’s visual function. Optic nerve heads and intraocular pressure were normal, but visual fields were suspect. The patient was advised to make an appointment with an ophthalmologist. Risk factors for development of PG and management of patients with PDS will be discussed.

Effects of Two Different Doses of Hirudin on APTT, Determined with Eight Different Reagents

1995 ◽  
Vol 73 (02) ◽  
pp. 219-222 ◽  
Author(s):  
Manuel Monreal ◽  
Luis Monreal ◽  
Rafael Ruiz de Gopegui ◽  
Yvonne Espada ◽  
Ana Maria Angles ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
In Vitro Study ◽  
Ex Vivo Model ◽  
Suitable Candidate ◽  
Significant Prolongation ◽  
High Doses ◽  
Different Doses

SummaryThe APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study.Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica- based reagents.In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica- containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.

Anti-Inflammatory Effects of Novel Standardized Platelet Rich Plasma Releasates on Knee Osteoarthritic Chondrocytes and Cartilage in vitro

2019 ◽  
Vol 20 (11) ◽  
pp. 920-933 ◽  
Author(s):  
Lucía Gato-Calvo ◽  
Tamara Hermida-Gómez ◽  
Cristina R. Romero ◽  
Elena F. Burguera ◽  
Francisco J. Blanco
Keyword(s):  
Gene Expression ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Cartilage Explants ◽  
Ex Vivo Model ◽  
Chondrocyte Viability ◽  
Platelet Concentration ◽  
The Absolute ◽  
Anti Inflammatory

Background: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. Objective: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. Methods: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1β (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1β (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. Results: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1β and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. Conclusion: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

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