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Veterinary ophthalmology2020; 23(5); 785-791; doi: 10.1111/vop.12782

Corneal and scleral permeability of Desmoteplase in different species.

Abstract: Intraocular fibrin clots caused by severe uveitis can be a sight-threatening condition that needs to be resolved quickly and reliably. Intracameral injection of tissue-plasminogen activator (tPA) is commonly used to resolve intraocular fibrin. However, the drug does not reach fibrinolytic concentrations after topical application. Desmoteplase (DSPA) is a structurally similar but smaller fibrinolytic agent with a higher fibrin selectivity, a longer half-life, and better biocompatibility compared with tPA. This study was designed to evaluate the corneal and scleral permeability of DSPA in rabbits, pigs, dogs, horses, and humans ex vivo. Methods: Corneal and scleral tissues (n = 5 per group) were inserted into Franz-type diffusion chambers and exposed to 1.4 mg/mL DSPA for 30 minutes. Drug concentrations on the receiver side were determined by liquid chromatography-tandem mass spectrometry. Results: Concentrations of DSPA after corneal and scleral permeation through fresh tissues ranged from 0.0 to 16.3 µg/mL and 0.0 to 11.4 µg/mL (rabbits), 0.3 to 5.6 µg/mL and 3.1 to 9.2 µg/mL (dogs), 2.1 to 14.9 µg/mL and 4 to 8.7 µg/mL (horses), and 0.6 to 3 µg/mL and 2.9 to 18.1 µg/mL (pigs), respectively. A concentration of 0.07-12.9 µg/mL DSPA was detectable after diffusion through tissue culture preserved human donor bank corneas (Table 1). Conclusions: Desmoteplase has the ability to permeate both cornea and sclera ex vivo in all species tested. Implications of the ex vivo permeability of DSPA suggest that in vivo permeability may be possible, and if so, it could lead to a novel topical application for lysing fibrin.
© 2020 American College of Veterinary Ophthalmologists.
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Publication Date: 2020-08-30 PubMed ID: 32862517DOI: 10.1111/vop.12782Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study discovered that Desmoteplase, a fibrinolytic agent, has the capacity to penetrate both the cornea and sclera in various animal species as well as in human tissue, which might result in a novel way of applying the drug to treat visual threatening conditions caused by intraocular fibrin clots.

Introduction

  • The research is centered on the treatment of intraocular fibrin clots that may cause sight-threatening situations in conditions like severe uveitis.
  • Traditionally, the commonly used means of resolving these fibrin clots is through an intraocular injection of tissue-plasminogen activator (tPA). This method has its limitations, though, as the drug does not reach fibrinolytic concentrations after topical application.
  • The study proposes the use of Desmoteplase (DSPA), a smaller fibrinolytic agent which has a higher fibrin selectivity, a longer half-life and better biocompatibility compared to tPA.

Methods

  • Different species including rabbits, pigs, dogs, horses, and humans were subjected to the study.
  • The researchers evaluated the permeability of DSPA in the corneal and scleral tissues of these species through an ex vivo experiment.
  • They inserted corneal and scleral tissues into Franz-type diffusion chambers and exposed the tissues to 1.4 mg/mL DSPA solution for 30 minutes.
  • They used liquid chromatography-tandem mass spectrometry to determine drug concentration on the receiver side.

Results

  • The results showed DSPA concentrations after corneal and scleral permeation through the fresh tissues of rabbits, dogs, horses and pigs fell within definite ranges, showing that DSPA was able to penetrate the tissues.
  • When using tissue culture preserved human donor bank corneas, DSPA was detectable after diffusion.

Conclusion

  • Based on these results, it was concluded that DSPA has the ability to permeate both the cornea and sclera of all species tested in the study.
  • These findings suggest the possibility of in vivo permeability, which indicates that DSPA could potentially be used in a novel way for the topical treatment for lysing fibrin, an application that could aid in the treatment of sight-threatening conditions.

Cite This Article

APA
Brütsch DR, Hunziker P, Pot S, Tappeiner C, Voelter K. (2020). Corneal and scleral permeability of Desmoteplase in different species. Vet Ophthalmol, 23(5), 785-791. https://doi.org/10.1111/vop.12782

Publication

Veterinary ophthalmology
ISSN: 1463-5224
NlmUniqueID: 100887377
Country: England
Language: English
Volume: 23
Issue: 5
Pages: 785-791

Researcher Affiliations

Brütsch, Deborah R
  • Ophthalmology Section, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Hunziker, Peter
  • Functional Genomics Center Zurich, University of Zurich, Zurich, Switzerland.
Pot, Simon
  • Ophthalmology Section, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Tappeiner, Christoph
  • Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Voelter, Katrin
  • Ophthalmology Section, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

MeSH Terms

  • Animals
  • Cornea / drug effects
  • Cornea / metabolism
  • Dogs
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / pharmacology
  • Horses
  • Humans
  • Ophthalmic Solutions
  • Permeability
  • Plasminogen Activators / administration & dosage
  • Plasminogen Activators / pharmacology
  • Rabbits
  • Sclera / drug effects
  • Sclera / metabolism
  • Species Specificity
  • Swine
  • Uveitis / drug therapy
  • Uveitis / veterinary

Grant Funding

  • ECVO

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Citations

This article has been cited 2 times.
  1. Piechowski-Jozwiak B, Abidi E, El Nekidy WS, Bogousslavsky J. Clinical Pharmacokinetics and Pharmacodynamics of Desmoteplase. Eur J Drug Metab Pharmacokinet 2022 Mar;47(2):165-176.
    doi: 10.1007/s13318-021-00743-8pubmed: 34893967google scholar: lookup
  2. Nápoles P, Faria M, Campos EJ. Porcine Corneal Models as Translational Platforms for Innovative Therapies: Current Insights and Future Directions. J Funct Biomater 2025 Dec 9;16(12).
    doi: 10.3390/jfb16120460pubmed: 41440637google scholar: lookup
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