A porcine ex vivo model of pigmentary glaucoma

Dang, Yalong; Waxman, Susannah; Wang, Chao; Loewen, Ralista T.; Sun, Ming; Loewen, Nils A.

doi:10.1101/118448

Cited by 13 publications

(53 citation statements)

References 72 publications

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“…With a baseline IOP of 11.64+/-1.45 mmHg [18], a minimum sample size of 7 is required to detect an 18% IOP reduction [23] with an alpha of 0.05 and a power of 0.80.…”

Section: Statisticsmentioning

confidence: 99%

“…The anterior segment perfusion culture followed our previous protocols [12,18,19]. Briefly, within two hours of sacrifice, fresh pig eyes from a local slaughterhouse were sterilized with 5% Betadine and subsequently bisected.…”

Section: Porcine Eye Perfusion Culture Iop and Outflow Facilitymentioning

confidence: 99%

“…Hematoxylin and eosin (H&E) staining was subsequently performed for the histology using a previous protocol [18].…”

Section: Histologymentioning

confidence: 99%

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Outflow Enhancement by Three Different ab Interno Trabeculectomy Procedures in a Porcine Anterior Segment Model

Dang¹,

Wang²,

Shah³

et al. 2018

Preprint

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Objective: To evaluate three different microincisional ab interno trabeculectomy procedures in a porcine eye perfusion model. Methods:In perfused porcine anterior segments, 90 degrees of trabecular meshwork (TM) were ablated using the Trabectome (T; n=8), Goniotome (G; n=8), or Kahook device (K; n=8). After 24 hours, additional 90 degrees of TM were removed. Intraocular pressure (IOP) and outflow facility were measured at 5 µl/min and 10 µl/min perfusion to simulate an elevated IOP. Structure and function were assessed with canalograms and histology.Results: At 5 µl/min infusion rate, T resulted in a greater IOP reduction than G or K from baseline (76.12% decrease versus 48.19% and 47.96%, P=0.013). IOP reduction between G and K was similar (P=0.420). Removing another 90 degrees of TM caused an additional IOP reduction only in T and G but not in K. Similarly, T resulted in the largest increase in outflow facility at 5 µl/min compared with G and K (first ablation: 3.41 times increase versus 1.95 and 1.87; second ablation: 4.60 versus 2.50 and 1.74) with similar results at 10 µl/min (first ablation: 3.28 versus 2.29 and 1.90 (P=0.001); second ablation: 4.10 versus 3.01 and 2.01 (P=0.001)). Canalograms indicated circumferential flow beyond the ablation endpoints.Conclusions: T, G and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.

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“…With a baseline IOP of 11.64+/-1.45 mmHg [18], a minimum sample size of 7 is required to detect an 18% IOP reduction [23] with an alpha of 0.05 and a power of 0.80.…”

Section: Statisticsmentioning

confidence: 99%

Section: Porcine Eye Perfusion Culture Iop and Outflow Facilitymentioning

confidence: 99%

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Outflow Enhancement by Three Different ab Interno Trabeculectomy Procedures in a Porcine Anterior Segment Model

Dang¹,

Wang²,

Shah³

et al. 2018

Preprint

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“…Unlike other ROCK inhibitors, RKI-1447 does not exhibit cross-reactivity with AKT, MEK, PKA, and PKG signaling, even at a high concentration of up to 10 μM 4,21 , reducing the risk of side effects. Recently, our group developed an ex vivo pigmentary glaucoma model that exhibited a IOP elevation, a typical TM stress fiber formation, and a reduction in TM phagocytosis 22,23 . In this paper, we examine the ocular hypotensive effect of RKI-1447 in an ex vivo anterior chamber perfusion model and investigate its possible mechanisms.…”

mentioning

confidence: 99%

Ocular Hypotension, Actin Stress Fiber Disruption and Phagocytosis Increase by RKI-1447, a Rho-Kinase Inhibitor

Dang¹,

Wang²,

Shah³

et al. 2018

Preprint

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Objective: The Rho GTPase/Rho kinase pathway is an important target in glaucoma treatment. This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor developed for cancer treatment, in a porcine ex vivo pigmentary glaucoma model. Materials and Methods:Twenty-eight fresh porcine anterior chambers were perfused with pigment medium (1.67×10 7 pigment particles/ml) for 48 hours before being subjected to the RKI-1447 (n=16) or the vehicle control (n=12). Another twelve eyes with normal medium perfusion served as the control. The intraocular pressure (IOP) was recorded at two-minute intervals and the outflow facility was calculated. To investigate the intracellular mechanism of the IOP reduction, primary trabecular meshwork cells were exposed to RKI-1447 or the vehicle control and then analyzed for changes in cytoskeleton, motility, and phagocytosis.

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“…In glaucomatous eyes, diseased TM has a reduced facility and shows reduced phagocytosis [25,26], increased stiffness [27], and stress fiber formation [26]. Either removing TM surgically [28] or rehabilitating TM function by stem cells [29] can restore normal outflow and decrease IOP in previous studies.…”

Section: Discussionmentioning

confidence: 99%

Two-Year Outcomes of Ab Interno Trabeculectomy with the Trabectome for Chinese Primary Open Angle Glaucoma: A Retrospective Multicenter Study

Dang¹,

Wang²,

Cen³

et al. 2018

Preprint

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To evaluate the 2-year efficacy and safety of ab interno trabeculectomy with the Trabectome in Chinese primary open-angle glaucoma (POAG) patients. This was a multicenter, retrospective study and included POAG patients with or without visually-significant cataracts. The primary outcome was intraocular pressure (IOP) reduction. Secondary outcomes included reduction of glaucoma medications, surgical complications, and success at 2-years. Success was defined as: 1) IOP < 21 mmHg and at least 20% IOP reduction from baseline after 3 months at any two consecutive visits, and 2) no additional glaucoma surgery required. A total of 42 patients were enrolled; thirteen had a history of failed glaucoma surgery. Twelve patients underwent Trabectome surgery combined with phacoemulsification while the remainder underwent Trabectome surgery alone. Overall, the mean preoperative IOP was 21.4±1.23 mmHg. The Trabectome lowered IOP to 18.5± 0.94 mmHg at 2 years (P<0.05). The number of glaucoma medications also decreased from a baseline of 2.0±0.9 to 1.2± 0.21 at 2 years (P=0.04). The overall success was 78%, with patients undergoing combined surgery having a higher success than those with Trabectome surgery alone (100% vs. 76%). No major complications were seen. The Trabectome appears to be an efficient and safe procedure in Chinese POAG patients in the longterm.

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A porcine ex vivo model of pigmentary glaucoma

Cited by 13 publications

References 72 publications

Outflow Enhancement by Three Different ab Interno Trabeculectomy Procedures in a Porcine Anterior Segment Model

Outflow Enhancement by Three Different ab Interno Trabeculectomy Procedures in a Porcine Anterior Segment Model

Ocular Hypotension, Actin Stress Fiber Disruption and Phagocytosis Increase by RKI-1447, a Rho-Kinase Inhibitor

Two-Year Outcomes of Ab Interno Trabeculectomy with the Trabectome for Chinese Primary Open Angle Glaucoma: A Retrospective Multicenter Study

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