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. 2024 Aug 27;13(17):5073.
doi: 10.3390/jcm13175073.

An Association between HTRA1 and TGF-β2 in the Vitreous Humor of Patients with Chorioretinal Vascular Diseases

Yoko Fukushima  1   2 , Shizuka Takahashi  1   3 , Machiko Nakamura  4 , Tatsuya Inoue  4 , Yusuke Fujieda  4 , Toshiyuki Sato  4 , Shingo Noguchi  4 , Motokazu Tsujikawa  5 , Hirokazu Sakaguchi  1   6 , Kohji Nishida  1   2
Affiliations

An Association between HTRA1 and TGF-β2 in the Vitreous Humor of Patients with Chorioretinal Vascular Diseases

Yoko Fukushima et al. J Clin Med. .

Abstract

Background: The aim of this paper was to investigate the protein concentrations of high-temperature requirement A 1 (HTRA1) and transforming growth factor-β (TGF-β) in the vitreous humor of patients with chorioretinal vascular diseases. Methods: This study measured protein concentrations of HTRA1, TGF-β1-3, and vascular endothelial growth factor A (hereinafter called VEGF) in the vitreous humor from seven eyes of patients with chorioretinal vascular diseases (age-related macular degeneration, diabetic macular edema, and retinal vein occlusion) and six control eyes (idiopathic epiretinal membrane and macular hole). We analyzed the mutual relationship among the protein levels. Results: The protein levels of HTRA1 and VEGF were significantly increased in the chorioretinal vascular disease group compared with the control group (1.57 ± 0.79 ×10-9 mol/mL vs. 0.68 ± 0.79 ×10-9 mol/mL, p = 0.039; 3447.00 ± 3423.47 pg/mL vs. 35.33 ± 79.01 pg/mL, p = 0.046, respectively). TGF-β2 levels were not significantly different between groups (2222.71 ± 1151.25 pg/mL for the chorioretinal vascular disease group vs. 1918.83 ± 744.01 pg/mL for the control group, p = 0.62). The concentration of HTRA1 was strongly associated with TGF-β2 levels in the vitreous humor, independent of VEGF (r = 0.80, p = 0.0010). Conclusions: We revealed that vitreous HTRA1 was increased in patients with chorioretinal vascular diseases and strongly correlated with TGF-β2.

Keywords: HTRA1; TGF-β; chorioretinal vascular disease.

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Conflict of interest statement

S. Takahashi and H. Sakaguchi declare no conflicts of interest. Y. Fukushima received financial support from Daiichi Sankyo Co., Ltd. and the JST FOREST Program (JPMJFR200S). M. Nakamura, T. Inoue, Y. Fujieda, T. Sato and S. Nocguhi are employees of Daiichi Sankyo Co., Ltd. T. Sato has patents in Daiichi Sankyo Co., Ltd. M. Tsujikawa. and K. Nishida received financial support from Daiichi Sankyo Co., Ltd.

Figures

Figure 1
Figure 1
The distribution of the individual vitreous concentrations of (A) HTRA1, (B) TGF-β2, (C) TGF-β3, and (D) VEGF by group. Note that HTRA1 levels were measured as 10−9 mol/L, and TGF-β2, TGF-β3, and VEGF were measured as pg/mL. p-values are indicated in the plots, * p < 0.05.
Figure 2
Figure 2
Scatter plots and linear regression lines of the concentrations of (A) TGF-β2 and HTRA1, (B) HTRA1 and VEGF, and (C) VEGF and TGF-β2. The equation, correlation coefficient, and statistical significance are provided in the plots, * p < 0.05.
Figure 3
Figure 3
Representative images obtained from patients with AMD and DME. The levels of HTRA1 and TGF-β2 are elevated in the eyes of patients with more severe hyperpermeability. The HTRA1, TGF-β2, and VEGF concentrations in the eyes are given below the images. FA in AMD cases (A,B) was obtained by SPECTRALIS® HRA (Heidelberg Engineering, Heidelberg, Germany), and in DME cases (C,D) by Optos® (Optos, Marlborough, MA, USA). OCT was obtained by SPECTRALIS for all disease types.
Figure 3
Figure 3
Representative images obtained from patients with AMD and DME. The levels of HTRA1 and TGF-β2 are elevated in the eyes of patients with more severe hyperpermeability. The HTRA1, TGF-β2, and VEGF concentrations in the eyes are given below the images. FA in AMD cases (A,B) was obtained by SPECTRALIS® HRA (Heidelberg Engineering, Heidelberg, Germany), and in DME cases (C,D) by Optos® (Optos, Marlborough, MA, USA). OCT was obtained by SPECTRALIS for all disease types.
See this image and copyright information in PMC

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