Assessment of Aqueous Humor Dynamics in the Rodent by Constant Flow Infusion

Millar, J. A.; Phan, Tien; Pang, Iok Hou

doi:10.1007/978-1-4939-7407-8_11

Cited by 6 publications

(5 citation statements)

References 9 publications

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“…essentially interfere with each other due to the disparity between the scales of their velocity and pressure fields. The radial flow does not significantly modify the velocity field of the natural convection, and this convection does not, as assumed by previous studies, alter the IOP [21,31,[43][44][45]. Table 3 and Fig 4 show the post-operative IOP values in the different scenarios.…”

Section: Plos Onesupporting

confidence: 58%

Numerical model to predict and compare the hypotensive efficacy and safety of minimally invasive glaucoma surgery devices

et al. 2020

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To predict and compare the hypotensive efficacy of three minimally-invasive glaucoma surgery (MIGS) implants through a numerical model. Methods Post-implant hypotensive efficacy was evaluated by using a numerical model and a computational fluid dynamics simulation. Three different devices were compared: the XEN 45 stent (tube diameter, 45 μm), the XEN 63 stent (63 μm) and the PreserFlo microshunt (70 μm). The influence of the filtration bleb pressure (Bp) and tube diameter, length, and position within the anterior chamber (AC) on intraocular pressure (IOP) were evaluated. Results Using baseline IOPs of 25, 30 and 50 mmHg, respectively, the corresponding computed post-implant IOPs for each device were as follows: XEN 45: 17 mmHg (29% decrease), 19 mmHg (45%) and 20 mmHg (59%) respectively; XEN 63: 13 mmHg (48%), 13 mmHg (62%), and 13 mmHg (73%); PreserFlo: 12 mmHg (59%), 13 mmHg (73%) and 13 mmHg (73%). At a baseline IOP of 35 mmHg with an increase in the outflow resistance within the Bp from 5 to 17 mmHg, the hypotensive efficacy for each device was reduced as follows: XEN45: 54% to 37%; XEN 63: 74% to 46%; and PreserFlo: 75% to 47%. The length and the position of the tube in the AC had only a minimal (non-significant) effect on IOP (<0.1 mmHg).

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Section: Plos Onesupporting

confidence: 58%

Numerical model to predict and compare the hypotensive efficacy and safety of minimally invasive glaucoma surgery devices

et al. 2020

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“…After IOP measurement on Day 21, animals were used for AH outflow facility measurement, performed using our previously published technique of constant flow infusion. 20 , 55 , 56 In brief, mice were anesthetized using a cocktail of ketamine/xylazine (induction: 100 mg/kg:10 mg/kg, intraperitoneally; maintenance: 1/2 × to 1/4 × induction dose). For local anesthesia, eyes were then given one drop of 0.5% proparacaine HCl (Alcaine).…”

Section: Methodsmentioning

confidence: 99%

ID1 and ID3 are Negative Regulators of TGFβ2-Induced Ocular Hypertension and Compromised Aqueous Humor Outflow Facility in Mice

Mody

Millar

Clark

2021

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.In POAG, elevated IOP remains the major risk factor in irreversible vision loss. Increased TGFβ2 expression in POAG aqueous humor and in the trabecular meshwork (TM) amplifies extracellular matrix (ECM) deposition and reduces ECM turnover in the TM, leading to a decreased aqueous humor (AH) outflow facility and increased IOP. Inhibitor of DNA binding proteins (ID1 and ID3) inhibit TGFβ2-induced fibronectin and PAI-1 production in TM cells. We examined the effects of ID1 and ID3 gene expression on TGFβ2-induced ocular hypertension and decreased AH outflow facility in living mouse eyes.METHODS. IOP and AH outflow facility changes were determined using a mouse model of Ad5-hTGFβ2 C226S/C288S -induced ocular hypertension. The physiological function of ID1 and ID3 genes were evaluated using Ad5 viral vectors to enhance or knockdown ID1/ID3 gene expression in the TM of BALB/cJ mice. IOP was measured in conscious mice using a Tonolab impact tonometer. AH outflow facilities were determined by constant flow infusion in live mice. RESULTS.Over-expressing ID1 and ID3 significantly blocked TGFβ2-induced ocular hypertension (P < 0.0001). Although AH outflow facility was significantly decreased in TGFβ2transduced eyes (P < 0.04), normal outflow facility was preserved in eyes injected concurrently with ID1 or ID3 along with TGFβ2. Knockdown of ID1 or ID3 expression exacerbated TGFβ2-induced ocular hypertension. CONCLUSIONS.Increased expression of ID1 and ID3 suppressed both TGFβ2-elevated IOP and decreased AH outflow facility. ID1 and/or ID3 proteins thus may show promise as future candidates as IOP-lowering targets in POAG.

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“…AH Outflow Facility Measurement. AH outflow facility (C) was measured in live anesthetized mice using constant-flow infusion method in a masked manner as described previously (27,(60)(61)(62) and in SI Appendix.…”

Section: Methodsmentioning

confidence: 99%

Impaired TRPV4-eNOS signaling in trabecular meshwork elevates intraocular pressure in glaucoma

Patel

Chen

Kasetti

et al. 2021

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

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Primary Open Angle Glaucoma (POAG) is the most common form of glaucoma that leads to irreversible vision loss. Dysfunction of trabecular meshwork (TM) tissue, a major regulator of aqueous humor (AH) outflow resistance, is associated with intraocular pressure (IOP) elevation in POAG. However, the underlying pathological mechanisms of TM dysfunction in POAG remain elusive. In this regard, transient receptor potential vanilloid 4 (TRPV4) cation channels are known to be important Ca2+ entry pathways in multiple cell types. Here, we provide direct evidence supporting Ca2+ entry through TRPV4 channels in human TM cells and show that TRPV4 channels in TM cells can be activated by increased fluid flow/shear stress. TM-specific TRPV4 channel knockout in mice elevated IOP, supporting a crucial role for TRPV4 channels in IOP regulation. Pharmacological activation of TRPV4 channels in mouse eyes also improved AH outflow facility and lowered IOP. Importantly, TRPV4 channels activated endothelial nitric oxide synthase (eNOS) in TM cells, and loss of eNOS abrogated TRPV4-induced lowering of IOP. Remarkably, TRPV4-eNOS signaling was significantly more pronounced in TM cells compared to Schlemm’s canal cells. Furthermore, glaucomatous human TM cells show impaired activity of TRPV4 channels and disrupted TRPV4-eNOS signaling. Flow/shear stress activation of TRPV4 channels and subsequent NO release were also impaired in glaucomatous primary human TM cells. Together, our studies demonstrate a central role for TRPV4-eNOS signaling in IOP regulation. Our results also provide evidence that impaired TRPV4 channel activity in TM cells contributes to TM dysfunction and elevated IOP in glaucoma.

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Assessment of Aqueous Humor Dynamics in the Rodent by Constant Flow Infusion

Cited by 6 publications

References 9 publications

Numerical model to predict and compare the hypotensive efficacy and safety of minimally invasive glaucoma surgery devices

Numerical model to predict and compare the hypotensive efficacy and safety of minimally invasive glaucoma surgery devices

ID1 and ID3 are Negative Regulators of TGFβ2-Induced Ocular Hypertension and Compromised Aqueous Humor Outflow Facility in Mice

Impaired TRPV4-eNOS signaling in trabecular meshwork elevates intraocular pressure in glaucoma

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