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Ajay Sharma, Marcos Reyes, Huiyi Chen, Nishant Sinha, Rajiv R Mohan; Decorin-PEI nanoparticles promote bleb survival by reducing fibrosis in rabbit glaucoma trabeculectomy model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2732.
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© ARVO (1962-2015); The Authors (2016-present)
Bleb-fibrosis causes glaucoma filtration surgery (GFS) failure due to excessive wound healing by TGFβ. Decorin, a small leucine-rich proteoglycan, is a natural inhibitor of TGFβ. We tested the hypothesis that decorin-PEI nanoparticles’ intraoperative application would block TGFβ hyperactivity, thus attenuate the excessive fibrosis and increase the bleb survival
Six New Zealand White rabbits were used for GFS. Bleb was made by creating a conjunctival flap over 2 mm2 sclerotomy. Decorin palsmid-PEI nanoconstruct (n=3) or balanced saline solution (n=3) was administered in rabbit eye intra-operatively via subconjunctival injection. Slit lamp biomicroscopy, clinical eye exams, and intraocular pressure (IOP) measurements with tonometer were performed on day 0, 3, 7 and 14 after the surgery. The stereomicroscopy quantified bleb size and vascularity (score 1-4). On postoperative day-14, eyes were enucleated and snap frozen in optimal cutting temperature medium after euthanasia. Serial sections of eye tissues were prepared and stained for H&E, α-smooth muscle actin (SMA; myofibroblast marker) and f- actin (activated fibroblast marker).
The rabbits receiving decorin gene delivery by nanoparticles exhibited significantly reduced bleb fibrosis compared to vehicle-treated controls (p<0.01). The increased bleb survival by decorin-PEI was evidenced by the significant increase in bleb-length and area (p<0.01), and decrease in bleb-vascularity (p<0.05). Decorin-PEI treated rabbit eyes exhibited lower IOP than controls. H&E histology revealed a notable decrease in fibrosis in large area of the bleb. Immunofluorescence analysis of serial sections demonstrated remarkably decreased SMA+ and F-actin+ cells in the bleb. No damage, pathology and/or adverse effects were noted in the rabbit eyes of each group
The intraoperative subconjunctival decorin-PEI injection significantly decreased fibrosis and increased bleb survival. Nanoparticle-mediated decorin gene therapy has potential to enhance bleb survival and provide long-term glaucoma management. More in vivo rabbit studies are warranted.
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