Prostaglandin F2α increases uveoscleral outflow in the cynomolgus monkey

Gabelt, B’Ann T.; Kaufman, Paul L.

doi:10.1016/0014-4835(89)90049-3

Cited by 229 publications

(90 citation statements)

References 17 publications

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“…We found that topical pilocarpine administered prior to the 7 th dose of twice daily application of PGF 2α blocked the IOP lowering effect of PGF 2α (Figure 9) . Subsequently, studies in my laboratory directly measuring uveoscleral outflow using fluoresceinated dextran and isotope accumulation techniques (Gabelt and Kaufman, 1989) and in Dr. Bill's laboratory indirectly measuring uveoscleral outflow using isotope dilution and accumulation techniques (Nilsson et al, 1989) showed that uveoscleral outflow in monkeys was increased 2-3 fold after multiple topical treatments (Gabelt and Kaufman, 1989) or by 60% after a single topical dose (Nilsson et al, 1989) of PGF 2α -isopropyl ester.…”

Section: Prostaglandins and Enhancement Of Uveoscleral Outflowmentioning

confidence: 99%

Enhancing trabecular outflow by disrupting the actin cytoskeleton, increasing uveoscleral outflow with prostaglandins, and understanding the pathophysiology of presbyopia

Kaufman

2008

Experimental Eye Research

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Several major areas of work by the author and his international collaborators are reviewed. 1) The ciliary muscle in the nonhuman primate eye was disinserted at the scleral spur. Pilocarpine was then ineffective in increasing outflow facility, indicating that ciliary muscle contraction mediated the IOPlowering effect of muscarinic cholinergics. 2) Compounds such as cytochalasins, H-7 and latrunculin A/B, which alter the actin cytoskeleton, cellular contractility and cellular adhesions in cultured trabecular meshwork cells, relaxed trabecular pathway cells and consequently the meshwork itself so as to decrease IOP and enhance trabecular outflow facility in nonhuman primates. Gene transfer approaches utilizing C3 and caldesmon over-expression by viral vectors to target specific steps in the cellular contractility/cytoskeleton/cell adhesion cascades characteristically altered trabecular meshwork cell morphology and increased outflow facility in organ-cultured anterior segments. 3) Prostaglandin F 2α analogues enhanced matrix metalloproteinase production by ciliary muscle cells and scleral fibroblasts, leading to remodeling of the extracellular matrix of the ciliary muscle and sclera and consequently to increased uveoslceral outflow and decreased IOP in primates. 4) The rhesus monkey was an excellent model for human presbyopia, losing the accommodative response to cholinergic stimulation in the same timeframe relative to lifespan. No changes were found in ciliary muscle enzymes involved in acetylcholine biosynthesis or degradation or in muscarinic receptor numbers or affinity. Contractility of isolated ciliary muscle did not diminish with age, but posterior ciliary muscle attachments stiffened, suggesting a possible role in restricting muscle and consequently lens movement during accommodation. A model to reproducibly stimulate accommodation through central stimulation of the Edinger-Westphal nucleus was developed. Goniovideography and ultrasound biomicroscopic techniques allowed real-time recording and analysis of the accommodation-relevant structures. Surgical ablation of the intraocular structures involved in the accommodation response has led to further understanding of their roles and changes with age related to presbyopia. 5) Global collaborations such as those involved in these studies will be essential in the future, as science becomes "bigger".Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The story I will tell is embodied in the title. It is about recognizing questions, asking how and why things happen, recognizing signs along the way, and about focus yet w...

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Section: Prostaglandins and Enhancement Of Uveoscleral Outflowmentioning

confidence: 99%

Enhancing trabecular outflow by disrupting the actin cytoskeleton, increasing uveoscleral outflow with prostaglandins, and understanding the pathophysiology of presbyopia

Kaufman

2008

Experimental Eye Research

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“…In normal living monkeys, trabecular outflow is pressure sensitive and uveoscleral outflow is comparatively pressure-insensitive when IOP is greater than 7 to 10 mmHg (Bill, 1966;1967). Although, under some circumstances, such as at low pressures (Bill, 1966;1967), inflammation (Toris and Pederson, 1987), or perhaps after treatment with prostaglandins (Gabelt and Kaufman, 1989), uveoscleral outflow may not be completely pressure insensitive, pressure-insensitive outflow typically represents primarily uveoscleral outflow. During perfusions with living monkeys, the average P 0 of pentobarbital-anesthetized monkeys is ∼7 mmHg (Erickson-Lamy et al, 1984).…”

Section: Living Monkey Eyesmentioning

confidence: 99%

Factors affecting outflow facility calculations

Tian

Gabelt

et al. 2006

Experimental Eye Research

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Outflow facility (C), a ratio of outflow rate (F) to relevant pressure, is an important indication of outflow resistance in the ocular drainage pathway. The higher the C, the lower the outflow resistance. According to the classic Goldmann equation, C=F/(IOP-P e )(IOP, intraocular pressure; P e , episcleral venous pressure). Since anterior chamber (AC) perfusions directly measure outflow and are less affected by scleral creep and rigidity or changes in uveal blood content than repeated tonography in living eyes, they are widely used to determine C in living animals or cultured anterior segments from enucleated eyes. Bárány (1964) initially developed the 2-level constant pressure perfusion technique for living monkey eyes to avoid possible influences of changes in eye parameters (e.g., P e , spontaneous IOP [P 0 ] or aqueous humor formation [AHF]) on C measurements. However, since these eye parameters do not exist in cultured anterior segments, 1-level constant pressure perfusion (Erickson-Lamy et al., 1991) and constant flow rate perfusion (Johnson and Tschumper, 1987) are typically used to determine C in organ culture. Based on different perfusion techniques, two basic formulas derived from the Goldmann equation are used to calculate C: (A) C=(F 2 -F 1 )/(P 2 -P 1 ), which is usually used in 2-level constant pressure perfusion either in living animals or in cultured anterior segments (F 1 or F 2 represents F at P 1 [lower perfusion pressure] or P 2 [higher perfusion pressure]); (B) C=F/P, which is usually used in 1-level constant pressure perfusion or constant flow rate perfusion in cultured anterior segments (P, perfusion pressure; P e is ignored in this formula because it is assumed to be zero in the cultured anterior segments). A comparison of C values calculated using Formula B and the data obtained during 2-level constant pressure perfusion in vivo or in vitro requires the following modifications: C=F 1 /(P 1 -P 0 ) or C=F 2 /(P 2 -P 0 ) where F 1 or F 2 is due to the change in pressure from P 0 to P 1 or P 2 (P 0 is assumed to be stable during short-term perfusions in vivo and is zero in vitro). C values from the same eye and the same perfusion are often quite different when calculated by the two formulas, since Formula A calculates C for the change in pressure from P 1 to P 2 , whereas Formula B calculates C either for the change in pressure from P 0 to P 1 or P 2 in living eyes or for a given pressure (P 1 or P 2 ) in cultured segments. However, the difference has not been clearly stated in previous studies, so that confusion might occur when comparing C values obtained by the two formulas. Additionally, C at different pressures may also be affected by factors physiologically unrelated to the formulas. To determine factors that may affect C values and to evaluate the significance of these factors in aqueous humor dynamics research, we compared C values calculated by Formulas A and B based on some previous perfusion experiments.

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“…[5][6][7] These agents have been shown to lower IOP mainly by increasing uveoscleral outflow. [8][9][10] However, Alvarado et al 11 showed in a translational model that prostaglandin analogues could have direct effects on the trabecular meshwork as well. Studies on the effects of medications and particularly prostaglandin analogue medications in SLT results are controversial.…”

Section: Introductionmentioning

confidence: 99%

The Influence of Topical Prostaglandin Analogues in Inflammation After Selective Laser Trabeculoplasty Treatment

Ayala

Chen²

2012

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Reducing intraocular pressure (IOP) seems to be the only treatment that slows progression in glaucoma. The IOP can be decreased by pharmaceutical treatment, laser [selective laser trabeculoplasty (SLT)] treatment, or surgery. Prostaglandin analogues have been postulated to share action mechanisms with SLT and to possibly diminish the effects of SLT treatment. The aim of the current study was to investigate the effects of prostaglandin analogues in inflammation and IOP reduction after SLT treatment. Methods: Prospective nonrandomized study. One hundred and eighteen patients were included in the study. Inclusion criteria: Glaucoma (open-angle or pseudoexfoliation glaucoma) patients who will be treated with SLT. Inflammation was measured with a laser flare meter (Kowa FM-500). Measurements were made before SLT and then 2 h, 1 week, and 1 month after SLT treatment. IOP was also checked at the same time intervals. The SLT treatment was performed over 90°. All patients were divided into two groups: those receiving prostaglandins analogues and those treated with nonprostaglandin analogues. Results: Inflammation before and after SLT showed no significant difference between the groups at all the time intervals studied (t-test, before: P = 0.16; 2 h: P = 0.14; 1 week: P = 0.12; and 1 month: P = 0.36). IOP reduction showed no significant difference between the groups (t-test, P = 0.31). Conclusions: SLT treatment effects do not seem to be influenced by the use of prostaglandin analogues.

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Prostaglandin F2α increases uveoscleral outflow in the cynomolgus monkey

Cited by 229 publications

References 17 publications

Enhancing trabecular outflow by disrupting the actin cytoskeleton, increasing uveoscleral outflow with prostaglandins, and understanding the pathophysiology of presbyopia

Enhancing trabecular outflow by disrupting the actin cytoskeleton, increasing uveoscleral outflow with prostaglandins, and understanding the pathophysiology of presbyopia

Factors affecting outflow facility calculations

The Influence of Topical Prostaglandin Analogues in Inflammation After Selective Laser Trabeculoplasty Treatment

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