Abstract
In this present study, we investigated the effect of a controlled release of anti-transforming growth factor β (TGF-β) antibody on intraocular pressure (IOP), bleb formation, and conjunctival scarring in a canine glaucoma filtration surgery model using gelatin hydrogel (GH). Glaucoma surgery models were made in 14 eyes of 14 beagles and divided into the following two groups: (1) subconjunctival implantation of anti-TGF-β antibody-loaded GH (GH-TGF-β group, n = 7), and (2) subconjunctival implantation of GH alone (GH group, n = 7). IOP and bleb features were then assessed in each eye at 2- and 4-weeks postoperative, followed by histological evaluation. We found that IOP was significantly reduced at 4-weeks postoperative in the two groups (p < 0.05) and that IOP in the GH-TGF-β-group eyes was significantly lower than that in the GH-group eyes (p = 0.006). In addition, the bleb score at 4-weeks postoperative was significantly higher in the GH-TGF-β group than in the GH group (p < 0.05), and the densities of fibroblasts, proliferative-cell nuclear antigen (PCNA)-positive cells, mast cells, and TGF-β-positive cells were significantly lower in the GH-TGF-β group than in the GH group. The findings of this study suggest that, compared with the GH-group eyes, implantation of anti-TGF-β antibody-loaded GH maintains IOP reduction and bleb formation by suppressing conjunctival scarring due to the proliferation of fibroblasts for a longer time period via a sustained release of anti-TGF-β antibody from GH.
Highlights
Glaucoma filtration surgery is a primary treatment for glaucoma that results in decreased intraocular pressure (IOP) by draining the aqueous humor to the subconjunctival space and forming a bleb
The conjunctival scarring response in trabeculectomy surgery is thought to be affected by the passage of the aqueous humor including growth factors such as transforming growth factor β (TGF-β), and subconjunctival scarring post glaucoma surgery is strongly affected by cytokines [11,12]
We investigated the effect of a sustained release of anti-TGF-β antibody from gelatin hydrogel (GH) in a canine glaucoma surgery model for IOP reduction and the effect on tissue in comparison with the application of GH alone
Summary
Glaucoma filtration surgery (i.e., trabeculectomy) is a primary treatment for glaucoma that results in decreased intraocular pressure (IOP) by draining the aqueous humor to the subconjunctival space and forming a bleb. Several previous studies have focused on subconjunctivally implanting DDSs to provide a sustained release of antiproliferative drugs over an extended time period post glaucoma surgery [24,25,26] Most of those studies reported that these DDSs maintained IOP reduction and prolonged bleb persistence to the same degree as the conventional application of MMC and 5-FU, while significantly reducing their toxicity. We previously reported the possibility of using GH containing chymase inhibitor and GH containing MMC for longer-term maintenance of filtering blebs and IOP reduction by the prolonged suppression of subconjunctival scarring [34,35] In this present study, we investigated the effect of a sustained release of anti-TGF-β antibody from GH in a canine glaucoma surgery model for IOP reduction and the effect on tissue in comparison with the application of GH alone
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