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Aqueous Humor Dynamics

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Carol B Toris – 1st expert on this subject based on the ideXlab platform

  • Chapter 7 Aqueous Humor Dynamics I. Measurement Methods and Animal Studies
    Current Topics in Membranes, 2020
    Co-Authors: Carol B Toris

    Abstract:

    Publisher Summary Intraocular pressure (IOP) is maintained by the Dynamics of ocular Aqueous Humor that involves its secretion, circulation throughout the anterior chamber, and drainage into the iridocorneal angle. The measurable components of Aqueous Humor Dynamics include Aqueous flow, outflow facility, uveoscleral outflow, and episcleral venous pressure. Multiple methods are available to assess these components. Interpretation of data collected by these methods requires an understanding of the inherent assumptions and limitations of each method applicable to the species of animal under investigation. Despite the inevitable problems associated with each method, invaluable information has been collected regarding normal circadian rhythms and interspecies differences in Aqueous Humor Dynamics. Additionally, studies of animal models of spontaneous and induced glaucoma have enhanced the understanding of human glaucoma and facilitated the design of improved pharmacological treatments and surgical procedures. This chapter describes various methods to assess Aqueous Humor Dynamics and summarizes findings from the animal species that have contributed the most to the understanding of Aqueous Humor Dynamics.

  • Chapter 8 Aqueous Humor Dynamics II: Clinical Studies
    Current Topics in Membranes, 2020
    Co-Authors: Carol B Toris, Carl B. Camras

    Abstract:

    Publisher Summary A stable rate of production and drainage of Aqueous Humor is essential for the health of the eye and maintenance of normal visual function. This chapter reviews the contributions of Aqueous Humor Dynamics in normal and pathological conditions affecting intraocular pressure (IOP). IOP remains relatively stable throughout one’s lifetime but subtle changes do occur in the outflow pathways that could increase IOP and the risk for glaucoma. Abnormalities in Aqueous Humor Dynamics have been found in various clinical syndromes that affect IOP. Most of the abnormalities have been localized to the Aqueous Humor outflow pathways. Surprisingly, Aqueous Humor production remains relatively stable in all of these conditions and ranges of IOPs. Some older drugs to treat elevated IOP work by reducing Aqueous Humor production, theoretically, placing the avascular lens and cornea at risk for damage from limited nutrients and accumulation of toxic metabolites. The recently approved drugs and the ones currently under development for future glaucoma therapy are those that target the outflow pathways. From a physiological perspective, this is a logical approach because this is the location of the pathology in glaucoma and the region in need of repair. These drugs and their effects on Aqueous Humor Dynamics also are discussed in this chapter.

  • Time dependent effects of sympathetic denervation on Aqueous Humor Dynamics and choroidal blood flow in rabbits
    Current Eye Research, 2020
    Co-Authors: Guilin Zhan, Carl B. Camras, David C. Ball, Corey J. Mayberger, Mark E. Tafoya, Carol B Toris

    Abstract:

    Purpose. This study investigates the time-dependent effects of superior cervical ganglionectomy (SCGx) on Aqueous Humor Dynamics and ocular blood flow in rabbits. Methods. Measurements were made at various times between 24 hours and 12 months after SCGx. Intraocular pressure (IOP) was measured by pneumatonometry, Aqueous flow by fluorophotometry and outflow facility by tonography. Uveoscleral outflow was determined by an intracameral tracer infusion technique and blood flow to the choroid was evaluated with fluorescent microspheres. Values in denervated eyes were compared with the contralateral, normallyinnervated eyes using a paired Student’s two-tailed t-test. Results. At 24 hours after SCGx, IOP in denervated eyes was less than in normally-innervated eyes (14.6 ± 0.8 vs 20.1 ± 1.5mmHg, 27%, p < 0.002). At one month, IOPs were not different between eyes. Compared with normally-innervated eyes at 10-12 months, IOP in denervated eyes was greater (20.4 ± 0.7 vs 17.2 ± 0.9mmHg, 19%, p < 0.001), outflo...

Paul L Kaufman – 2nd expert on this subject based on the ideXlab platform

  • effects of vitrectomy and lensectomy on older rhesus macaques oxygen distribution antioxidant status and Aqueous Humor Dynamics
    Investigative Ophthalmology & Visual Science, 2017
    Co-Authors: Carla J Siegfried, Yingbo Shui, Baohe Tian, Michael T Nork, Gregg A Heatley, Paul L Kaufman

    Abstract:

    Purpose: The purpose of this study is to evaluate effects of vitrectomy (PPV) and lens extraction with intraocular lens implantation (PE/IOL) on molecular oxygen (pO2) distribution, Aqueous Humor antioxidant-oxidant balance, Aqueous Humor Dynamics, and histopathologic changes in the trabecular meshwork (TM) in the older macaque monkey. Methods: Six rhesus monkeys underwent PPV followed by PE/IOL. pO2, outflow facility, and intraocular pressure (IOP) were measured. Aqueous and vitreous Humor specimens were analyzed for antioxidant status and 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative damage. TM specimens were obtained for immunohistochemical and quantitative PCR analysis. Results: pO2 at baseline revealed steep gradients in the anterior chamber and low levels in the posterior chamber (PC) and around the lens. Following PPV and PE/IOL, pO2 significantly increased in the PC, around the IOL, and angle. IOP increased following both surgical interventions, with no change in outflow facility. Histopathologic analysis did not show changes in TM cell quantification, but there was an increase in 8-OHdG. Quantitative PCR did not reveal significant differences in glaucoma-related gene expression. Aqueous and vitreous Humor analysis revealed decreased ascorbate and total reactive antioxidant potential and increased 8-OHdG in the Aqueous Humor only in the surgical eyes. Conclusions: Oxygen distribution in the older rhesus monkey is similar to humans at baseline and following surgical interventions. Our findings of histopathologic changes of TM oxidative damage and alterations in the oxidant-antioxidant balance suggest a potential correlation of increased oxygen exposure with oxidative stress/damage and the development of open angle glaucoma.

  • Effects of Vitrectomy and Lensectomy on Older Rhesus Macaques: Oxygen Distribution, Antioxidant Status, and Aqueous Humor Dynamics
    Investigative Ophthalmology & Visual Science, 2017
    Co-Authors: Carla J Siegfried, Yingbo Shui, Baohe Tian, Gregg A Heatley, T. Michael Nork, Paul L Kaufman

    Abstract:

    The purpose of this study is to evaluate effects of vitrectomy (PPV) and lens extraction with intraocular lens implantation (PE/IOL) on molecular oxygen (pO2) distribution, Aqueous Humor antioxidant-oxidant balance, Aqueous Humor Dynamics, and histopathologic changes in the trabecular meshwork (TM) in the older macaque monkey.
    Six rhesus monkeys underwent PPV followed by PE/IOL. pO2, outflow facility, and intraocular pressure (IOP) were measured. Aqueous and vitreous Humor specimens were analyzed for antioxidant status and 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative damage. TM specimens were obtained for immunohistochemical and quantitative PCR analysis.
    pO2 at baseline revealed steep gradients in the anterior chamber and low levels in the posterior chamber (PC) and around the lens. Following PPV and PE/IOL, pO2 significantly increased in the PC, around the IOL, and angle. IOP increased following both surgical interventions, with no change in outflow facility. Histopathologic analysis did not show changes in TM cell quantification, but there was an increase in 8-OHdG. Quantitative PCR did not reveal significant differences in glaucoma-related gene expression. Aqueous and vitreous Humor analysis revealed decreased ascorbate and total reactive antioxidant potential and increased 8-OHdG in the Aqueous Humor only in the surgical eyes.
    Oxygen distribution in the older rhesus monkey is similar to humans at baseline and following surgical interventions. Our findings of histopathologic changes of TM oxidative damage and alterations in the oxidant-antioxidant balance suggest a potential correlation of increased oxygen exposure with oxidative stress/damage and the development of open angle glaucoma.

  • Aqueous Humor Dynamics in monkeys in response to the kappa opioid agonist bremazocine
    Transactions of the American Ophthalmological Society, 2007
    Co-Authors: Carol A Rasmussen, Bann T Gabelt, Paul L Kaufman

    Abstract:

    Purpose: To determine the effects of the kappa opioid agonist, bremazocine (BRE), on intraocular pressure (IOP) and Aqueous Humor Dynamics in normotensive cynomolgus monkeys. Methods: IOP, pupil diameter, refraction, Aqueous Humor flow, and mean arterial pressure (MAP) were measured following unilateral topical application of 1 to 100 µg BRE. IOP and MAP responses to 100 µg BRE were repeated during intravenous infusion of angiotensin II (ATII). IOP and MAP responses to BRE were also measured following pretreatment with the opioid receptor antagonists norbinaltorphimine (nor-BNI) or naloxone. Outflow facility was measured following unilateral intracameral exchange with 0.01 to 100 µg/mL BRE. IOP, Aqueous Humor flow, pupil, and MAP were measured after unilateral intracameral bolus injection of 1 µg of BRE. Results: Unilateral topical BRE caused a dose-related reduction in IOP and Aqueous Humor flow in both eyes and in MAP. Pupil miosis occurred at the 100-µg dose. There was no effect on refraction. IOP and MAP decreases after 100 µg of BRE were eliminated by ATII infusion. Differential IOP effects after 10-µg topical BRE doses were not eliminated by nor-BNI or naloxone. Unilateral intracameral bolus injection of BRE decreased IOP in both eyes but had no effect on MAP or Aqueous Humor flow. Outflow facility was unchanged after intracameral exchange with BRE. Conclusions: The IOP response to high doses of BRE in monkeys can be attributed to peripheral or central effects on MAP. The IOPlowering response to topical BRE is due to Aqueous Humor flow suppression via non-opioid receptor stimulation. Some components of the IOP response are mediated by unknown mechanisms.

José Melena – 3rd expert on this subject based on the ideXlab platform

  • A comparative study of topical natural ergot alkaloids on the intraocular pressure and Aqueous Humor Dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits
    Graefe's Archive for Clinical and Experimental Ophthalmology, 2007
    Co-Authors: Gustavo Puras, Juan Santafé, José Segarra, Manuel Garrido, José Melena

    Abstract:

    Background Although it has been suggested that ergot derivatives may play a role in antiglaucoma therapy, little attention has been paid to the ocular hypotensive action of these drugs. Having previously reported that topical natural ergot alkaloids ergocristine α-ergocryptine and ergocornine dose-dependently reduce intraocular pressure in ocular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits, the aim of the present work was to compare the effect of ergocristine, α-ergocryptine and ergocornine on the intraocular pressure and Aqueous Humor Dynamics in ocular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits, in order to further explore the ocular actions of these compounds. Methods Experiments were conducted in albino ocular normotensive and hypertensive rabbits by intracameral injection of α-chymotrypsin. Intraocular pressure responses to drug vehicle and seven different doses of topical natural ergot alkaloids were examined, in order to obtain dose–response relationships for comparing the intraocular pressure-lowering effect and potency of these drugs. Tonographies were also performed to ascertain the actions of natural ergot alkaloids on Aqueous Humor Dynamics. Results All natural ergot alkaloids tested reduced intraocular pressure in a dose-related fashion. The ocular hypotensive effect was greater in α-chymotrypsin-induced ocular hypertensive rabbits for the three compounds tested. All natural ergot alkaloids tested decreased both tonographic outflow facility and, to a greater extent, Aqueous Humor inflow in ocular normotensive and in α-chymotrypsin-induced ocular hypertensive rabbits. Conclusion Taken together, our data suggest that these compounds decrease both tonographic outflow facility and, to a greater extent, Aqueous Humor inflow, which explains their final effect in ocular normotensive and in α-chymotrypsin-induced ocular hypertensive rabbits. Reductions in Aqueous Humor inflow observed after topical application of natural ergot alkaloids in α-chymotrypsin-induced ocular hypertensive rabbits can only be explained by a marked inhibition of active secretion of Aqueous Humor, since processes involved in Aqueous Humor formation may probably be altered after α-chymotrypsin injection.

  • A comparative study of topical natural ergot alkaloids on the intraocular pressure and Aqueous Humor Dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits
    Graefes Archive for Clinical and Experimental Ophthalmology, 2007
    Co-Authors: Gustavo Puras, Juan Santafé, José Segarra, Manuel Garrido, José Melena

    Abstract:

    Background
    Although it has been suggested that ergot derivatives may play a role in antiglaucoma therapy, little attention has been paid to the ocular hypotensive action of these drugs. Having previously reported that topical natural ergot alkaloids ergocristine α-ergocryptine and ergocornine dose-dependently reduce intraocular pressure in ocular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits, the aim of the present work was to compare the effect of ergocristine, α-ergocryptine and ergocornine on the intraocular pressure and Aqueous Humor Dynamics in ocular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits, in order to further explore the ocular actions of these compounds.

  • The effect of topical natural ergot alkaloids on the intraocular pressure and Aqueous Humor Dynamics in rabbits with α-chymotrypsin-induced ocular hypertension
    Graefe's Archive for Clinical and Experimental Ophthalmology, 2002
    Co-Authors: Gustavo Puras, Juan Santafé, José Segarra, Manuel Garrido, José Melena

    Abstract:

    Background: We previously reported that topical natural ergot alkaloids ergocristine, α-ergocryptine and ergocornine dose-dependently reduce intraocular pressure in ocular normotensive rabbits, most likely by decreasing Aqueous Humor inflow. In the present study, the effects of these compounds on intraocular pressure and Aqueous Humor Dynamics in a rabbit model for ocular hypertension were assessed. Methods: Experiments were conducted in albino rabbits made ocular hypertensive by intracameral injection of α-chymotrypsin. Intraocular pressure responses to drug vehicle and seven different doses of topical natural ergot alkaloids were examined in order to obtain dose–response relationships for comparing the intraocular pressure-lowering effect and potency of these drugs. Tonographies were also performed to ascertain the actions of natural ergot alkaloids on Aqueous Humor Dynamics in α-chymotrypsin-induced ocular hypertensive rabbits. Results: Topical application of the natural ergot alkaloids ergocristine, α-ergocryptine and ergocornine lowered intraocular pressure in α-chymotrypsin-induced ocular hypertensive rabbits in a dose-related fashion, with ergocristine displaying the greatest intraocular pressure-lowering effect. Tonographic studies revealed a decrease in the tonographic outflow facility following topical application of natural ergot alkaloids, although only the effects of both ergocristine and α-ergocryptine reached statistical significance. All natural ergot alkaloids tested significantly reduced the calculated Aqueous Humor inflow. Conclusion: This study suggests that the natural ergot alkaloids ergocristine, α-ergocryptine and ergocornine effectively decrease intraocular pressure in the α-chymotrypsin-induced model of ocular hypertension. Since these compounds reduce the tonographic Aqueous Humor outflow facility, their final ocular antihypertensive effect appears to result from a remarkable reduction of the Aqueous Humor inflow.