Tosi Gian Marco, Caldi Elena, Neri Giovanni, Nuti Elisabetta, Marigliani Davide, Baiocchi Stefano, Traversi Claudio, Cevenini Gabriele, Tarantello Antonio, Fusco Fiorella, Nardi Federica, Orlandini Maurizio, Galvagni Federico
Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):162-167. doi: 10.1167/iovs.16-20922.
The purpose of this study was to evaluate the expression of high-temperature requirement A serine peptidase 1 (HTRA1), TGF-β1, bone morphogenetic protein 4 (BMP4), growth differentiation factor 6 (GDF6), and VEGFA proteins in the aqueous humor of patients with naïve choroidal neovascularization (nCNV) secondary to AMD.
We measured by ELISA the concentrations of HTRA1, TGF-β1, BMP4, GDF6, and VEGFA in the aqueous humor of 23 patients affected by nCNV who received three consecutive monthly intravitreal injections of 0.5 mg ranibizumab. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). Twenty-three age-matched cataract patients served as controls.
Bone morphogenetic protein 4 and GDF6 were not detectable in any samples. Baseline HTRA1 was higher than controls (P < 0.0001) and higher than both the month 1 (P < 0.0001) and the month 2 (P < 0.0001) values. Baseline VEGFA was higher than controls (P < 0.0001), not different from month 1 value (P = 0.0821), but higher than month 2 value (P < 0.0001). Baseline TGF-β1 was higher than controls (P = 0.0015) and not different from month 1 (P = 0.129) and month 2 values (P = 0.5529). No correlation was found in naïve patients between concentrations of HTRA1 and TGF-β1, HTRA 1 and VEGFA, or TGF-β1 and VEGFA.
In nCNV patients, HTRA1 and TGF-β1 were significantly higher compared to controls. After treatment, TGF-β1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-β1 and HTRA1 in neovascular AMD and a VEGFA-independent role for TGF-β1.
本研究旨在评估年龄相关性黄斑变性（AMD）继发初发性脉络膜新生血管（nCNV）患者房水中高温需求A丝氨酸蛋白酶1（HTRA1）、转化生长因子-β1（TGF-β1）、骨形态发生蛋白4（BMP4）、生长分化因子6（GDF6）和血管内皮生长因子A（VEGFA）蛋白的表达。
我们采用酶联免疫吸附测定（ELISA）法，检测了23例接受连续3个月每月1次玻璃体内注射0.5mg雷珠单抗治疗的nCNV患者房水中HTRA1、TGF-β1、BMP4、GDF6和VEGFA的浓度。样本在基线（首次注射前）、第1个月（第二次注射前）和第2个月（第三次注射前）采集。23例年龄匹配的白内障患者作为对照。
在所有样本中均未检测到骨形态发生蛋白4和GDF6。基线时HTRA1高于对照组（P<0.0001），且高于第1个月（P<0.0001）和第2个月（P<0.0001）的值。基线时VEGFA高于对照组（P<0.0001），与第1个月的值无差异（P=0.0821），但高于第2个月的值（P<0.0001）。基线时TGF-β1高于对照组（P=0.0015），与第1个月（P=0.129）和第2个月的值无差异（P=0.5529）。在初发性患者中，未发现HTRA1与TGF-β1、HTRA1与VEGFA或TGF-β1与VEGFA浓度之间存在相关性。
在nCNV患者中，HTRA1和TGF-β1显著高于对照组。治疗后，TGF-β1持续升高，而HTRA1恢复到对照水平，提示TGF-β1和HTRA1参与新生血管性AMD，且TGF-β1具有不依赖VEGFA的作用。
