ArticleInvestigative ophthalmology & visual science2017
Effect of Cromakalim Prodrug 1 (CKLP1) on Aqueous Humor Dynamics and Feasibility of Combination Therapy With Existing Ocular Hypotensive Agents.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Preclinical Evaluation of Safety and Efficacy of QLS-111: A Novel Formulation of an Adenosine Triphosphate-Sensitive Potassium Channel Opener.Ophthalmology science · 2026Article
- Relationship Between Diurnal Variations of Episcleral Venous Pressure and Intraocular Pressure.Investigative ophthalmology & visual science · 2025Article
- Human Anterior Segment Perfusion Organ Culture.Methods in molecular biology (Clifton, N.J.) · 2025Article
- KThe Journal of pharmacology and experimental therapeutics · 2023Article
- Preclinical Pharmacokinetic Profile of Topical Ophthalmic and Intravenous Delivery of QLS-101, a Novel ATP-Sensitive Potassium Channel Opening Ocular Hypotensive Agent.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023Article
- Evaluation of neural innervation in the human conventional outflow pathway distal to Schlemm's canal.Experimental eye research · 2022Review
- Measurement of postmortem outflow facility using iPerfusion.Experimental eye research · 2022Article
- Morphological changes to Schlemm's canal and the distal aqueous outflow pathway in monkey eyes with laser-induced ocular hypertension.Experimental eye research · 2022Article
- Ocular Hypotensive Properties and Biochemical Profile of QLS-101, a Novel ATP-Sensitive Potassium (KATP) Channel Opening Prodrug.Investigative ophthalmology & visual science · 2022Article
- Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.Investigative ophthalmology & visual science · 2022Review
- Effect of ATP-sensitive Potassium Channel Openers on Intraocular Pressure in Ocular Hypertensive Animal Models.Investigative ophthalmology & visual science · 2022Article
- Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility.PloS one · 2022Article
- Pharmacological Profile and Ocular Hypotensive Effects of Cromakalim Prodrug 1, a Novel ATP-Sensitive Potassium Channel Opener, in Normotensive Dogs and Nonhuman Primates.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2021Article
- Vascular Aspects in Glaucoma: From Pathogenesis to Therapeutic Approaches.International journal of molecular sciences · 2021Review
- The β4-Subunit of the Large-Conductance Potassium Ion Channel KCa1.1 Regulates Outflow Facility in Mice.Investigative ophthalmology & visual science · 2020Article
- Pharmacological and pharmacokinetic profile of the novel ocular hypotensive prodrug CKLP1 in Dutch-belted pigmented rabbits.PloS one · 2020Article
- Structure-Function Changes of the Porcine Distal Outflow Tract in Response to Nitric Oxide.Investigative ophthalmology & visual science · 2018Article
- Pharmacological regulation of outflow resistance distal to Schlemm's canal.American journal of physiology. Cell physiology · 2018Article
- Subconjunctival Administration of an Adeno-Associated Virus Expressing Stanniocalcin-1 Provides Sustained Intraocular Pressure Reduction in Mice.Ophthalmology scienceArticle
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Purpose: Cromakalim prodrug 1 (CKLP1) is a water-soluble ATP-sensitive potassium channel opener that has shown ocular hypotensive properties in ex vivo and in vivo experimental models. To determine its mechanism of action, we assessed the effect of CKLP1 on aqueous humor dynamics and in combination therapy with existing ocular hypotensive agents. Methods: Outflow facility was assessed in C57BL/6 mice by ex vivo eye perfusions and by in vivo constant flow infusion following CKLP1 treatment. Human anterior segments with no trabecular meshwork were evaluated for effect on pressure following CKLP1 treatment. CKLP1 alone and in combination with latanoprost, timolol, and Rho kinase inhibitor Y27632 were evaluated for effect on intraocular pressure in C57BL/6 mice and Dutch-belted pigmented rabbits. Results: CKLP1 lowered episcleral venous pressure (control: 8.9 ± 0.1 mm Hg versus treated: 6.2 ± 0.1 mm Hg, P < 0.0001) but had no detectable effect on outflow facility, aqueous humor flow rate, or uveoscleral outflow. Treatment with CKLP1 in human anterior segments without the trabecular meshwork resulted in a 50% ± 9% decrease in pressure, suggesting an effect on the distal portion of the conventional outflow pathway. CKLP1 worked additively with latanoprost, timolol, and Y27632 to lower IOP, presumably owing to combined effects on different aspects of aqueous humor dynamics. Conclusions: CKLP1 lowered intraocular pressure by reducing episcleral venous pressure and lowering distal outflow resistance in the conventional outflow pathway. Owing to this unique mechanism of action, CKLP1 works in an additive manner to lower intraocular pressure with latanoprost, timolol, and Rho kinase inhibitor Y27632.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.