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...
Autores principales: | , , , , , , |
---|---|
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 |