Maeda Michiko, Kojima Shota, Sugiyama Tetsuya, Jin Denan, Takai Shinji, Oku Hidehiro, Kohmoto Ryohsuke, Ueki Mari, Ikeda Tsunehiko
Department of Ophthalmology, Osaka Medical College, Takatsuki-City, Osaka 569-8686, Japan.
Nakano Eye Clinic of Kyoto Medical Cooperative, Kyoto 604-8404, Japan.
Int J Mol Sci. 2017 May 5;18(5):985. doi: 10.3390/ijms18050985.
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, = 7), and (2) subconjunctival implantation of GH alone (GH group, = 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 ( < 0.05) and that IOP in the GH-TGF-β-group eyes was significantly lower than that in the GH-group eyes ( = 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 ( < 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.
在本研究中,我们在犬青光眼滤过手术模型中使用明胶水凝胶(GH)研究了抗转化生长因子β(TGF-β)抗体控释对眼压(IOP)、滤过泡形成和结膜瘢痕形成的影响。在14只比格犬的14只眼中建立青光眼手术模型,并分为以下两组:(1)结膜下植入负载抗TGF-β抗体的GH(GH-TGF-β组,n = 7),以及(2)结膜下单独植入GH(GH组,n = 7)。然后在术后2周和4周评估每只眼睛的IOP和滤过泡特征,随后进行组织学评估。我们发现两组术后4周时IOP均显著降低(P < 0.05),且GH-TGF-β组眼睛的IOP显著低于GH组眼睛(P = 0.006)。此外,GH-TGF-β组术后4周时的滤过泡评分显著高于GH组(P < 0.05),且GH-TGF-β组中纤维母细胞、增殖细胞核抗原(PCNA)阳性细胞、肥大细胞和TGF-β阳性细胞的密度显著低于GH组。本研究结果表明,与GH组眼睛相比,植入负载抗TGF-β抗体的GH通过从GH持续释放抗TGF-β抗体,更长时间地抑制因纤维母细胞增殖导致的结膜瘢痕形成,从而维持眼压降低和滤过泡形成。