| Objective: To investigate the efficacy and feasibility of mitomycin C drug delivery system(MMC DDS ) as a new glaucoma anti-scarring agent by observing its effects on a rabbit model of glaucoma filtration surgery and side effects on eyelid,conjunctiva,cornea,and anterior champer of rabbit eye.Methods:①Synthetic of mitomycin C drug delivery system:The material of drug delivery system is a polymer polylactioglycolic acid (PLGA) of polylactic acid (PLA) and polyglycolic acid (PGA).0.02mg mitomgcin C was incorporated into a membranous PLGA with a shape of circular cylinder, 1.0×2.0mm,oxford grey.The membraneous PLGA will dissolve within 28 days. ②In a randomized, prospective, maskend-observer study,filtering surgery was performed in both eyes of 24 New Zealand white rabbits,weighing 2.0-2.5kg and aged 12 to 14 weeks.The all right eyes received MMC DDS, 12 left eyes only received DDS randomly;the remaining 12 left eyes received 0.2mg/ml MMC in operation. ③ Tolerance and safety of MMC DDS in subscleral-flap administration were investigated by assessment of local toxicity,using clinical parameters such as anterior chamber activityjid edema,chemosis,hemorrhage,and corneal toxicity.④Effects on conjunctival scarring and filtration surgery outcome of MMC DDS were evaluated by observations of the bleb scope,height,the intraocular pressure(IOP) and the aqueous humor MMC concentrations were measured by high performance liquid chromatography(HPLC).⑤The New ZealandWhite rabbits were killed on days 7,14,28 after surgery. Both eyes were enucleated and histologically analyzed to observe inflammatory cells, fibroblasts in surgery sites of rabbit eyes.?Tissue sections were immunohistochemically stained for proliferating cell nuclear antigen(PCNA) protein express of fibroblast in surgery sites of rabbit eyes.Results:?Placements of MMC DDS in surgery sites were well tolerated in surgery eyes of New Zealand White rabbits. No intraocular inflammation was seen in any rabbit at any time in the study. ?MMC DDS was associated with successful filtration surgery, evidenced by bleb morphology compared with control group, the IOP remained consistently lower than baseline measurements in the MMC DDS group (p<0.01) .The implantation of MMC DDS can raise the MMC concentration of aqueous and remained for a long period. MMC concentration in aqueous was well above the ID50 of rabbit subconjunctival fibroblast and was well below the level known to cause endothelium toxicity and retinal toxicity. (3) MMC DDS appeared to be associated with reduced scarring activity at a microscopic level. ?MMC DDS reduced fibroblast activity, with a significantly reduction in the number and expression of PCNA of fibroblast.Conclusions :(1) MMC DDS can release MMC sustainly and slowly for a long period of time after surgery, which has strong effects on reduction inflammatory cells activity and fibroblast activity in surgery sites. MMC DDS was found to improve glaucoma filtration Surgery outcome.(2) During the whole time in this study, MMC DDS expressed no toxicity and side-effects. It has potential as a new safe and effective anti-scarring agent for easy use in glaucoma filtration surgery. |
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