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Systhesizing RGD Peptide Hydrogel To Inhibit Scarring After Glaucomatous Filtering Surgery

Posted on:2011-07-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:L LiangFull Text:PDF
GTID:1114360305492349Subject:Ophthalmology
Abstract/Summary:PDF Full Text Request
Objective:To evaluation the biocompatibility of novel peptide hydrogel. Methods:A peptide containing a RGD (arginine-glycine-aspartic acid) sequence as well as a hydrophobic N-fluorenyl-9-methoxycarbonyl (FMOC) tail was prepared via a standard FMOC solid phase peptide synthesis (SPPS) technique. The supramolecular self-assembly of such peptide throughπ-πstacking from FMOC tail can transfer the peptide aqueous solution into a three-dimensional hydrogel. The biocompatibility of the peptide hydrogel was evaluated via clinical follow-up and histological analysis. Results:The data obtained demonstrated that the peptide hydrogel exhibited good biocompatibility when injected to the subconjunctival space and anterior chamber of rabbit. Conclusions:These fundings indicate a potential application in ophthalmology as an implantable drug delivery system for the treatment to ocular anterior segment diseases such as glaucoma, iridocyclitis, and keratopathy. Objective:To design a means of providing controlling of postoperative intraocular pressure (IOP), longer bleb duration, and a normalizing wound healing after filtering surgery by subconjunctival injections of a novel self-assembled peptide hydrogel. Methods:A novel self-assembly hydrogel was prepared. Two animal experiments were performed:(1) Injecting the peptide hydrogel in subconjunctival space after filtering surgery of rabbit eye, the level of connective tissue growth factor (CTGF) mRNA were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) technique. (2) IOP, slit lamp biomicroscopy, ultrasound biomicroscopy (UBM), and histology sections were acquired after filtering surgery. Results:The level of CTGF mRNA as well as the mean IOP were significantly lower than that of the control eyes within postoperative 21 days. Images of bleb and UBM showed the patent bleb and filtration fistula in the surgical site. Pathological analysis hinted the filtering surgical wound healing was a normal healing process. Conclusion:This novel kind of peptide hydrogel may decrease CTGF mRNA of level, prolong the bled duration, and inhibit scar formation that serves to maintain decreased IOP after filtering surgery. This new approach, making use of a peptide hydrogel to normalize filtering surgical wound healing, may have the potential to prevent filtering surgery failure. Objective:An implanted drug delivery system can provide a localized and sustained release of drug over an extended period. We investigated the function of self-assembled peptide hydrogel as a subconjunctivally implanted drug carrier to inhibit the formation of postoperative scarring. Methods:After intraoperative administration of 5-Fu loaded peptide hydrogel to rabbit eyes, conjunctival hyperemia, corneal edema, duration of bleb and mean intraocular pressure (IOP) of rabbit eyes were evaluated. The status of bleb and filtration fistula formed after the filtering surgery was also examined via pathology and immunohistochemistry. Results:Due to the sustained release of 5-Fu from the peptide hydrogel to prevent the scleral flap fibrosis efficiently, the bleb and filtration fistula was patent without the presence of postoperative scarring, resulting in the mean intraocular pressure (IOP) of the rabbit eyes maintaining significantly lower within postoperative 28 days. Conclusions:Due to the sustained release of 5-Fu from the peptide hydrogel, the strategy demonstrated in this study had potential advantages including providing convenience and preventing the toxicity of 5-Fu to the surrounding ocular tissues efficiently, suggesting a feasibility of the peptide hydrogel as an implanted drug delivery system for the inhibition of postoperative scarring formation.
Keywords/Search Tags:Peptide, Self-assembly, Hydrogel, Biocompatibility, Self-assembly, Peptide hydrogel, Filtering surgery, Glaucoma, Peptide hydrogel, Drug delivery system, Inhibition of scarring formation
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