Prevention of ocular scarring post glaucoma filtration surgery using the inflammatory cell and platelet binding modulator saratin in a rabbit model

• Published in: PloS one Vol. 7; no. 4; p. e35627
• Main Authors: Min, Jeff, Lukowski, Zachary L, Levine, Monica A, Meyers, Craig A, Beattie, Ashley R, Schultz, Gregory S, Samuelson, Don A, Sherwood, Mark B
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.04.2012; Public Library of Science (PLoS)
• Subjects: 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; Florida; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035627

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.