Cargando…

Tissue Plasminogen Activator Effects on Fibrin Volume and the Ocular Proteome in a Juvenile Rabbit Model of Lensectomy

PURPOSE: To investigate the use of tissue plasminogen activator (tPA) and its effects on the ocular proteome as a therapeutic intervention for postoperative inflammation and fibrin formation following intraocular lens (IOL) insertion in a juvenile rabbit model. METHODS: Twenty-six rabbits, 6 to 7 we...

Descripción completa

Detalles Bibliográficos
Autores principales: Young, Jonathon B., Buchberger, Amanda Rae, Bogaard, Joseph D., Luecke, Linda Berg, Runquist, Matthew, Skumatz, Christine M. B., Kassem, Iris S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662573/
https://www.ncbi.nlm.nih.gov/pubmed/34874448
http://dx.doi.org/10.1167/tvst.10.14.7
_version_ 1784613466059833344
author Young, Jonathon B.
Buchberger, Amanda Rae
Bogaard, Joseph D.
Luecke, Linda Berg
Runquist, Matthew
Skumatz, Christine M. B.
Kassem, Iris S.
author_facet Young, Jonathon B.
Buchberger, Amanda Rae
Bogaard, Joseph D.
Luecke, Linda Berg
Runquist, Matthew
Skumatz, Christine M. B.
Kassem, Iris S.
author_sort Young, Jonathon B.
collection PubMed
description PURPOSE: To investigate the use of tissue plasminogen activator (tPA) and its effects on the ocular proteome as a therapeutic intervention for postoperative inflammation and fibrin formation following intraocular lens (IOL) insertion in a juvenile rabbit model. METHODS: Twenty-six rabbits, 6 to 7 weeks old, underwent lensectomy with IOL insertion. Following examination on day 3, 100 µL of either 25 µg of recombinant rabbit tPA or balanced salt solution (control) was injected into the anterior chamber. On postoperative day 4, rabbits underwent examination, and eyes were harvested and fixed for 9.4-Tesla magnetic resonance imaging (MRI). Three masked observers quantified fibrin scar volume using Horos Project software. Aqueous humor (AH) was collected immediately prior to surgery and on postoperative days 3 and 4. Proteins related to coagulation and inflammation were assessed in AH samples using targeted mass spectrometry via parallel reaction monitoring. RESULTS: tPA significantly reduced the volume of fibrin 24 hours following administration compared with control eyes (0.560 mm(3) vs. 3.29 mm(3); P < 0.0001). Despite the reduced fibrin scar, proteins related to the coagulation and complement cascade were not significantly different following tPA injection. CONCLUSIONS: tPA may be a safe candidate for reduction of postoperative fibrin scarring after intraocular surgery. MRI can provide a quantitative value for fibrin volume changes. TRANSLATIONAL RELEVANCE: tPA is a candidate to treat ocular fibrin scarring. MRI can quantify the efficacy of treatments in future dose-response studies. Targeted mass spectrometry can provide critical data necessary to help decipher the effect on the abundance of targeted proteins following pharmacological intervention.
format Online
Article
Text
id pubmed-8662573
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher The Association for Research in Vision and Ophthalmology
record_format MEDLINE/PubMed
spelling pubmed-86625732021-12-27 Tissue Plasminogen Activator Effects on Fibrin Volume and the Ocular Proteome in a Juvenile Rabbit Model of Lensectomy Young, Jonathon B. Buchberger, Amanda Rae Bogaard, Joseph D. Luecke, Linda Berg Runquist, Matthew Skumatz, Christine M. B. Kassem, Iris S. Transl Vis Sci Technol Article PURPOSE: To investigate the use of tissue plasminogen activator (tPA) and its effects on the ocular proteome as a therapeutic intervention for postoperative inflammation and fibrin formation following intraocular lens (IOL) insertion in a juvenile rabbit model. METHODS: Twenty-six rabbits, 6 to 7 weeks old, underwent lensectomy with IOL insertion. Following examination on day 3, 100 µL of either 25 µg of recombinant rabbit tPA or balanced salt solution (control) was injected into the anterior chamber. On postoperative day 4, rabbits underwent examination, and eyes were harvested and fixed for 9.4-Tesla magnetic resonance imaging (MRI). Three masked observers quantified fibrin scar volume using Horos Project software. Aqueous humor (AH) was collected immediately prior to surgery and on postoperative days 3 and 4. Proteins related to coagulation and inflammation were assessed in AH samples using targeted mass spectrometry via parallel reaction monitoring. RESULTS: tPA significantly reduced the volume of fibrin 24 hours following administration compared with control eyes (0.560 mm(3) vs. 3.29 mm(3); P < 0.0001). Despite the reduced fibrin scar, proteins related to the coagulation and complement cascade were not significantly different following tPA injection. CONCLUSIONS: tPA may be a safe candidate for reduction of postoperative fibrin scarring after intraocular surgery. MRI can provide a quantitative value for fibrin volume changes. TRANSLATIONAL RELEVANCE: tPA is a candidate to treat ocular fibrin scarring. MRI can quantify the efficacy of treatments in future dose-response studies. Targeted mass spectrometry can provide critical data necessary to help decipher the effect on the abundance of targeted proteins following pharmacological intervention. The Association for Research in Vision and Ophthalmology 2021-12-07 /pmc/articles/PMC8662573/ /pubmed/34874448 http://dx.doi.org/10.1167/tvst.10.14.7 Text en Copyright 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Article
Young, Jonathon B.
Buchberger, Amanda Rae
Bogaard, Joseph D.
Luecke, Linda Berg
Runquist, Matthew
Skumatz, Christine M. B.
Kassem, Iris S.
Tissue Plasminogen Activator Effects on Fibrin Volume and the Ocular Proteome in a Juvenile Rabbit Model of Lensectomy
title Tissue Plasminogen Activator Effects on Fibrin Volume and the Ocular Proteome in a Juvenile Rabbit Model of Lensectomy
title_full Tissue Plasminogen Activator Effects on Fibrin Volume and the Ocular Proteome in a Juvenile Rabbit Model of Lensectomy
title_fullStr Tissue Plasminogen Activator Effects on Fibrin Volume and the Ocular Proteome in a Juvenile Rabbit Model of Lensectomy
title_full_unstemmed Tissue Plasminogen Activator Effects on Fibrin Volume and the Ocular Proteome in a Juvenile Rabbit Model of Lensectomy
title_short Tissue Plasminogen Activator Effects on Fibrin Volume and the Ocular Proteome in a Juvenile Rabbit Model of Lensectomy
title_sort tissue plasminogen activator effects on fibrin volume and the ocular proteome in a juvenile rabbit model of lensectomy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662573/
https://www.ncbi.nlm.nih.gov/pubmed/34874448
http://dx.doi.org/10.1167/tvst.10.14.7
work_keys_str_mv AT youngjonathonb tissueplasminogenactivatoreffectsonfibrinvolumeandtheocularproteomeinajuvenilerabbitmodeloflensectomy
AT buchbergeramandarae tissueplasminogenactivatoreffectsonfibrinvolumeandtheocularproteomeinajuvenilerabbitmodeloflensectomy
AT bogaardjosephd tissueplasminogenactivatoreffectsonfibrinvolumeandtheocularproteomeinajuvenilerabbitmodeloflensectomy
AT lueckelindaberg tissueplasminogenactivatoreffectsonfibrinvolumeandtheocularproteomeinajuvenilerabbitmodeloflensectomy
AT runquistmatthew tissueplasminogenactivatoreffectsonfibrinvolumeandtheocularproteomeinajuvenilerabbitmodeloflensectomy
AT skumatzchristinemb tissueplasminogenactivatoreffectsonfibrinvolumeandtheocularproteomeinajuvenilerabbitmodeloflensectomy
AT kassemiriss tissueplasminogenactivatoreffectsonfibrinvolumeandtheocularproteomeinajuvenilerabbitmodeloflensectomy