Prevention of ocular scarring post glaucoma filtration surgery using the inflammatory cell and platelet binding modulator saratin in a rabbit model
Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer, more targeted, anti-fibrosis agents are sought. The protein saratin has been shown to exhibit anti-fibrotic and anti-thrombotic properties in response to injury, b...
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Published in | PloS one Vol. 7; no. 4; p. e35627 |
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Abstract | Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer, more targeted, anti-fibrosis agents are sought.
The protein saratin has been shown to exhibit anti-fibrotic and anti-thrombotic properties in response to injury, but had not been used for glaucoma surgery. The goal of this study was to compare the efficacy of saratin with that of the widely accepted mitomycin-C (MMC) in prolonging bleb survival following GFS in the rabbit model. Two saratin delivery routes were compared; a single intraoperative topical application versus a combination of intraoperative topical application with two additional postoperative injections.
Twenty-four New Zealand White rabbits underwent GFS and received either intraoperative topical saratin, intraoperative topical saratin plus two injections on post-operative days 4 and 8, balanced saline solution (BSS), or MMC. The bleb tissues and their elevation durations were compared based on clinical and histological findings.
Rabbits receiving topical+injections of saratin had a mean bleb survival of 33.6±8.5 days, significantly higher than the negative BSS controls, which averaged 17.4±6.0 days (p = 0.018). No improvement over BSS was seen for rabbits receiving topical saratin only (15.5±4.8 days, p = 0.749). Rabbits receiving saratin did not develop bleb avascularity and thinning associated with MMC treatment and there were no apparent clinical signs of toxicity.
Treatment with a single intraoperative topical application plus two additional postoperative injections significantly prolonged bleb elevation comparable to MMC, but without toxicity; however, topical application alone was ineffective. |
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AbstractList | Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer, more targeted, anti-fibrosis agents are sought. The protein saratin has been shown to exhibit anti-fibrotic and anti-thrombotic properties in response to injury, but had not been used for glaucoma surgery. The goal of this study was to compare the efficacy of saratin with that of the widely accepted mitomycin-C (MMC) in prolonging bleb survival following GFS in the rabbit model. Two saratin delivery routes were compared; a single intraoperative topical application versus a combination of intraoperative topical application with two additional postoperative injections. Twenty-four New Zealand White rabbits underwent GFS and received either intraoperative topical saratin, intraoperative topical saratin plus two injections on post-operative days 4 and 8, balanced saline solution (BSS), or MMC. The bleb tissues and their elevation durations were compared based on clinical and histological findings. Rabbits receiving topical+injections of saratin had a mean bleb survival of 33.6±8.5 days, significantly higher than the negative BSS controls, which averaged 17.4±6.0 days (p = 0.018). No improvement over BSS was seen for rabbits receiving topical saratin only (15.5±4.8 days, p = 0.749). Rabbits receiving saratin did not develop bleb avascularity and thinning associated with MMC treatment and there were no apparent clinical signs of toxicity. Treatment with a single intraoperative topical application plus two additional postoperative injections significantly prolonged bleb elevation comparable to MMC, but without toxicity; however, topical application alone was ineffective. Clinical Relevance Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer, more targeted, anti-fibrosis agents are sought. Objectives The protein saratin has been shown to exhibit anti-fibrotic and anti-thrombotic properties in response to injury, but had not been used for glaucoma surgery. The goal of this study was to compare the efficacy of saratin with that of the widely accepted mitomycin-C (MMC) in prolonging bleb survival following GFS in the rabbit model. Two saratin delivery routes were compared; a single intraoperative topical application versus a combination of intraoperative topical application with two additional postoperative injections. Methods Twenty-four New Zealand White rabbits underwent GFS and received either intraoperative topical saratin, intraoperative topical saratin plus two injections on post-operative days 4 and 8, balanced saline solution (BSS), or MMC. The bleb tissues and their elevation durations were compared based on clinical and histological findings. Results Rabbits receiving topical+injections of saratin had a mean bleb survival of 33.6±8.5 days, significantly higher than the negative BSS controls, which averaged 17.4±6.0 days (p = 0.018). No improvement over BSS was seen for rabbits receiving topical saratin only (15.5±4.8 days, p = 0.749). Rabbits receiving saratin did not develop bleb avascularity and thinning associated with MMC treatment and there were no apparent clinical signs of toxicity. Conclusions Treatment with a single intraoperative topical application plus two additional postoperative injections significantly prolonged bleb elevation comparable to MMC, but without toxicity; however, topical application alone was ineffective. Clinical Relevance Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer, more targeted, anti-fibrosis agents are sought. Objectives The protein saratin has been shown to exhibit anti-fibrotic and anti-thrombotic properties in response to injury, but had not been used for glaucoma surgery. The goal of this study was to compare the efficacy of saratin with that of the widely accepted mitomycin-C (MMC) in prolonging bleb survival following GFS in the rabbit model. Two saratin delivery routes were compared; a single intraoperative topical application versus a combination of intraoperative topical application with two additional postoperative injections. Methods Twenty-four New Zealand White rabbits underwent GFS and received either intraoperative topical saratin, intraoperative topical saratin plus two injections on post-operative days 4 and 8, balanced saline solution (BSS), or MMC. The bleb tissues and their elevation durations were compared based on clinical and histological findings. Results Rabbits receiving topical+injections of saratin had a mean bleb survival of 33.6±8.5 days, significantly higher than the negative BSS controls, which averaged 17.4±6.0 days (p = 0.018). No improvement over BSS was seen for rabbits receiving topical saratin only (15.5±4.8 days, p = 0.749). Rabbits receiving saratin did not develop bleb avascularity and thinning associated with MMC treatment and there were no apparent clinical signs of toxicity. Conclusions Treatment with a single intraoperative topical application plus two additional postoperative injections significantly prolonged bleb elevation comparable to MMC, but without toxicity; however, topical application alone was ineffective. Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer, more targeted, anti-fibrosis agents are sought. The protein saratin has been shown to exhibit anti-fibrotic and anti-thrombotic properties in response to injury, but had not been used for glaucoma surgery. The goal of this study was to compare the efficacy of saratin with that of the widely accepted mitomycin-C (MMC) in prolonging bleb survival following GFS in the rabbit model. Two saratin delivery routes were compared; a single intraoperative topical application versus a combination of intraoperative topical application with two additional postoperative injections. Twenty-four New Zealand White rabbits underwent GFS and received either intraoperative topical saratin, intraoperative topical saratin plus two injections on post-operative days 4 and 8, balanced saline solution (BSS), or MMC. The bleb tissues and their elevation durations were compared based on clinical and histological findings. Rabbits receiving topical+injections of saratin had a mean bleb survival of 33.6±8.5 days, significantly higher than the negative BSS controls, which averaged 17.4±6.0 days (p = 0.018). No improvement over BSS was seen for rabbits receiving topical saratin only (15.5±4.8 days, p = 0.749). Rabbits receiving saratin did not develop bleb avascularity and thinning associated with MMC treatment and there were no apparent clinical signs of toxicity. Treatment with a single intraoperative topical application plus two additional postoperative injections significantly prolonged bleb elevation comparable to MMC, but without toxicity; however, topical application alone was ineffective. |
Audience | Academic |
Author | Samuelson, Don A Lukowski, Zachary L Schultz, Gregory S Sherwood, Mark B Min, Jeff Beattie, Ashley R Meyers, Craig A Levine, Monica A |
AuthorAffiliation | 2 Department of Ob/Gyn and Institute of Wound Healing, College of Medicine, University of Florida, Gainesville, Florida, United States of America Massachusetts Eye & Ear Infirmary, Harvard Medical School, United States of America 3 College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States of America 1 Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, United States of America |
AuthorAffiliation_xml | – name: 1 Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, United States of America – name: Massachusetts Eye & Ear Infirmary, Harvard Medical School, United States of America – name: 3 College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States of America – name: 2 Department of Ob/Gyn and Institute of Wound Healing, College of Medicine, University of Florida, Gainesville, Florida, United States of America |
Author_xml | – sequence: 1 givenname: Jeff surname: Min fullname: Min, Jeff organization: Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, United States of America – sequence: 2 givenname: Zachary L surname: Lukowski fullname: Lukowski, Zachary L – sequence: 3 givenname: Monica A surname: Levine fullname: Levine, Monica A – sequence: 4 givenname: Craig A surname: Meyers fullname: Meyers, Craig A – sequence: 5 givenname: Ashley R surname: Beattie fullname: Beattie, Ashley R – sequence: 6 givenname: Gregory S surname: Schultz fullname: Schultz, Gregory S – sequence: 7 givenname: Don A surname: Samuelson fullname: Samuelson, Don A – sequence: 8 givenname: Mark B surname: Sherwood fullname: Sherwood, Mark B |
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DocumentTitleAlternate | Use of Saratin to Prevent Scarring Post GFS |
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Notes | Conceived and designed the experiments: ZLL JM MBS. Performed the experiments: ZLL JM MAL CAM ARB MBS. Analyzed the data: JM MAL ZLL. Contributed reagents/materials/analysis tools: GSS DAS. Wrote the paper: MAL JM ZLL MBS. |
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Snippet | Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer, more targeted,... Clinical Relevance Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer,... Clinical Relevance Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer,... |
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SubjectTerms | Administration, Topical Analysis Animals Antimetabolites Biology Blood Platelets - drug effects Cell adhesion & migration Cicatrix - etiology Cicatrix - prevention & control Collagen Complications Disease Models, Animal Drug dosages Eye - drug effects Eye - pathology Eye surgery Fibroblasts Fibrosis Fibrosis - etiology Fibrosis - prevention & control Filtering Surgery - adverse effects Filtration Glaucoma Glaucoma - pathology Glaucoma - surgery Growth factors Homocysteine Humans Inflammation Injections, Intraocular Medical research Medicine Mitomycin - administration & dosage Mitomycin - therapeutic use Mitomycin C Ophthalmology Prevention Proteins Rabbits Salivary Proteins and Peptides - administration & dosage Salivary Proteins and Peptides - therapeutic use Scars Surgery Survival Thrombosis - etiology Thrombosis - prevention & control Tissues Topical application Toxicity Transdermal drug delivery systems Wound healing |
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Title | Prevention of ocular scarring post glaucoma filtration surgery using the inflammatory cell and platelet binding modulator saratin in a rabbit model |
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