AIM: To measure the depths of different regions of the anterior chamber(AC) in healthy Chinese adults, and to explore possible correlations with age or gender.METHODS: The AC was imaged by swept-source optical coheren...AIM: To measure the depths of different regions of the anterior chamber(AC) in healthy Chinese adults, and to explore possible correlations with age or gender.METHODS: The AC was imaged by swept-source optical coherence tomography in healthy Chinese adults. The horizontal scan of the right eye was used to measure the anterior chamber depth(ACD) at 199 points.RESULTS: A total of 309 images from 309 subjects were analyzed. The ACD values at nearly all locations were negatively correlated with age(all P<0.05), except for ACD1, 2, 198, and 199(correspond to the iris roots). The mean annual decrease 0.013±0.005 mm/y for all ACDs combined, 0.008±0.004 mm/y for the peripheral region, 0.017±0.003 mm/y for the middle peripheral region, and 0.014±0.001 mm/y for the central region. The mean annual decrease was significantly different among these three regions(P<0.001). The ACD was greater in males than in females(P<0.05). The mean difference in ACD between males and females was 0.081±0.025 mm.CONCLUSION: This study showed that optical coherence tomography can be used to measure the ACD of different regions of the AC. We found reductions in ACD with age, although the reduction varied among different points, in healthy Chinese adults.展开更多
AIM: To evaluate the safety, quality and prospects of day-case cataract surgery performed in a Jiangsu public tertiary hospital METHODS: The general and clinical data for patients who underwent day-case cataract surge...AIM: To evaluate the safety, quality and prospects of day-case cataract surgery performed in a Jiangsu public tertiary hospital METHODS: The general and clinical data for patients who underwent day-case cataract surgery between August 1, 2014 and December 31, 2016 at this hospital were collected. The incidences of intraoperative and postoperative complications, preoperative and postoperative bestcorrected visual acuities(BCVAs), delayed discharge rate, rate of unplanned re-admission to hospital, and patient satisfaction were analyzed. RESULTS: A total of 4151 patients received cataract phacoemulsification surgery to correct age-related, congenital, traumatic, or complicated cataracts. Of these, age-related cataracts were the most frequently occurring. Patient age ranged from 18 to 101 y and the vast majority of patients were between 60 and 80 years old. Of the 4151 patients, 64.73%(2687/4151) had a systemic disease. The number of patients increased over the years, with the average number of patients per month being 90.4, 124.83, and 183.42 in 2014, 2015 and 2016, respectively. The average preoperative BCVA was 0.102±0.057 and average postoperative BCVAs at 1 d, 1 wk, and 1 mo post surgery were 0.453±0.264, 0.657±0.285, and 0.734±0.244, respectively. For intraoperative complications, 4.12%(171/4151) had posterior capsule rupture, 0.79%(33/4151) had iris or ciliary body injury, and 0.048%(2/4151) had suprachoroidal hemorrhage. For postoperative complications, 4.38%(182/4151) had cornea edema, 7.78%(323/4151) had intraocular hypertension, 0.096%(4/4151) had IOL toxicity syndrome, 0.28%(12/4151) had retained lens cortex, and 0.048%(2/4151) had hyphema. The delayed discharge rate was 0.82%(44/4151) and the unplanned re-admission to the hospital was 0(0/4151). The patient satisfaction rate was 91.42%(3795/4151). CONCLUSION: Day-case cataract surgery is safe and effective with good prospects for development.展开更多
AIM: To investigate changes in the rabbit retina after shortterm and small amounts tamponade of perfluorooctane(PFO).METHODS: New Zealand rabbits were used, and 48 eyes were randomly and evenly assigned into four diff...AIM: To investigate changes in the rabbit retina after shortterm and small amounts tamponade of perfluorooctane(PFO).METHODS: New Zealand rabbits were used, and 48 eyes were randomly and evenly assigned into four different groups. The PFO groups received a residue of 0.1 mL of PFO for ophthalmic surgery or 0.1 mL of F-Octane at the end of surgery; eyes from the pars plana vitrectomy(PPV) group were filled with balanced salt solution and those having not received surgical intervention served as controls. Eyes were collected at 1, 4 and 12 wk and studied.RESULTS: Under a microscope, nuclear counts of the inner nuclear layer(INL) and outer nuclear layer(ONL) did not differ among the four groups at all time points; however, slight disarrangement of the ONL and occasional vacuolization of the INL were found in the inferior retina only at 12 wk in two PFO groups. Four of the groups had similar results of Caspase-3 and TNF-α staining at all time points. Alternatively, IL-8 was increased in PFOa and PPV control groups at 4 wk and in all three PPV groups at 12 wk; also, the apoptotic index(%) was similarly increased in all three PPV groups at 4 and 12 wk.CONCLUSION: Both PFOs are well tolerated in rabbit eyes for up to 12 wk, which suggests that they can be used safely as intraoperative tools or for short-term and small amounts tamponade after surgery.展开更多
AIM: To investigate the clinical and optical coherence tomography(OCT) features of focal choroidal excavation(FCE) complicated with choroidal neovascularization(CNV) in young and middle aged patients. METHODS: We perf...AIM: To investigate the clinical and optical coherence tomography(OCT) features of focal choroidal excavation(FCE) complicated with choroidal neovascularization(CNV) in young and middle aged patients. METHODS: We performed a retrospective review of 26 patients with FCE accompanied by CNV. All patients underwent a complete ophthalmic examination. We analyzed the clinical characteristics of patients, focusing on the spectral-domain OCT features. All patients received intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF) agents. And we assessed the changes of central retinal thickness and best-corrected visual acuity(BCVA) after anti-VEGF therapy. RESULTS: The mean age of 26 patients was 35.5±7.3 y(range, 21-48 y). Of the 26 FCE lesions, 11 were located subfoveal, 6 were parafoveal, and 9 were extrafoveal. The mean FCE depth was 129.8±50.3 μm, and the mean width was 901.3±306.0 μm. The FCE depth was correlated positively with the width, but not correlated with age or refractive error. CNV was located within the excavation(19 eyes) or adjacent to the excavation(7 eyes). After anti-VEGF therapy, the central retinal thickness was significantly reduced and the BCVA was significantly improved. In the absorption process of subretinal fluid, we found that the fluid in the excavations needed to be absorbed at the last. A small amount of residual fluid could still be seen in a few deep excavations even after a longterm follow-up.CONCLUSION: FCE may be an important reason to cause CNV. Especially in young patients with idiopathic CNV, we should pay attention to the use of OCT to check the presence of FCE. Anti-VEGF therapy is generally effective for CNV associated with FCE.展开更多
Background: The demonstrated role of mitogen-activated protein kinase (MAPK) in both cell apoptosis and the inflammation pathway makes it an attractive target for photoreceptor protection. The aim of this study was to...Background: The demonstrated role of mitogen-activated protein kinase (MAPK) in both cell apoptosis and the inflammation pathway makes it an attractive target for photoreceptor protection. The aim of this study was to investigate the protective effects of MAPK antagonists against photoreceptor degeneration and retinal inflammation in a rat model of light-induced retinal degeneration. Methods:Sprague Dawley rats were treated with intravitreal injections of MAPK antagonists,inhibitors of p-P38,phosphorylated?extracellular regulated kinase (p-ERK) 1/2, and p-c-Jun N-terminal kinase (JNK) just before they were assigned to dark adaptation.After dark adaptation for 24 h, rats were exposed to blue light (2500 lux) in a light box for 24 h, and then returned to the normal 12-h light/12-h dark cycle. Samples were collected at different time points. MAPK expression during light exposure was examined with immunofluorescence. Photoreceptor death was detected with histopathology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of retinal p-ERK1/2, caspase 3, activated caspase 3, tumor necrosis factor (TNF)-α, and interleukin (IL)-1βwas examined by Western blotting. Differences between groups were evaluated using unpaired one-way analysis of variance and least significant difference post hoc tests. Results: MAPKs (P38, ERK1/2, and p-JNK) were phosphorylated and activated in the light injury groups, compared with normal group, and their expressions were mainly elevated in the outer nuclear layer (ONL). Among the selected MAPK antagonists, only the p-ERK1/2 inhibitor attenuated the loss of photoreceptors and the thinning of ONL in light injury groups. Besides, p-ERK1/2 inhibitor refrained light-induced photoreceptor apoptosis, which was presented by TUNELpositive cells. Light injury significantly increased the expression of p-ERK1/2 (1.12 ± 0.06 vs. 0.57 ± 0.08, t = 9.99, P < 0.05; 1.23 ± 0.03 vs. 0.57 ± 0.08, t = 11.90, P < 0.05; and 1.12 ± 0.12 vs. 0.57 ± 0.08, t = 9.86, P < 0.05; F = 49.55, P < 0.001), and induced caspase 3 activating (0.63 ± 0.06 vs. 0.14 ± 0.05, t = 13.67, P < 0.05; 0.74 ± 0.05 vs. 0.14 ± 0.05, t = 16.87, P < 0.05; and 0.80 ± 0.05 vs. 0.14 ± 0.05, t = 18.57, P < 0.05; F = 100.15, P < 0.001), compared with normal group. The p-ERK1/2 inhibitor significantly reduced p-ERK1/2 overexpression (0.61 ± 0.06 vs. 1.12 ± 0.06, t = -9.26, P < 0.05; 0.77 ± 0.06 vs. 1.23 ± 0.03, t = -8.29, P < 0.05; and 0.68 ± 0.03 vs. 1.12 ± 0.12, t = -7.83, P < 0.05; F = 49.55, P < 0.001) and downregulated caspase 3 activating (0.23 ± 0.04 vs. 0.63 ± 0.06, t = -11.24, P < 0.05; 0.43 ± 0.03 vs. 0.74 ± 0.05, t = -8.86, P < 0.05; and 0.58 ± 0.03 vs. 0.80 ± 0.05, t = -6.17, P < 0.05; F = 100.15, P < 0.001), compared with light injury group. No significant change in the total level of caspase 3 was seen in different groups (F = 0.56, P = 0.75). As for inflammation, light injury significantly increased the expression of TNF-α (0.42 ± 0.04 vs. 0.25 ± 0.05, t = 5.99, P < 0.05; 0.65 ± 0.03 vs. 0.25 ± 0.05, t = 14.87, P < 0.05; and 0.86 ± 0.04 vs. 0.25 ± 0.05, t = 22.58, P < 0.05; F = 160.27, P < 0.001) and IL-1β (0.24 ± 0.01 vs. 0.19 ± 0.02, t = 2.33, P < 0.05; 0.35 ± 0.02 vs. 0.19 ± 0.02, t = 7.97, P < 0.05; and 0.48 ± 0.04 vs. 0.19 ± 0.02, t = 14.69, P < 0.05; F = 77.29, P < 0.001), compared with normal group. P-ERK1/2 inhibitor significantly decreased the overexpression of TNF-α (0.22 ± 0.02 vs. 0.42 ± 0.04, t = -7.40, P < 0.05; 0.27 ± 0.02 vs. 0.65 ± 0.03, t = -14.27, P < 0.05; and 0.33 ± 0.03 vs. 0.86 ± 0.04, t = -19.58, P < 0.05; F = 160.27, P < 0.001) and IL?1β (0.13 ± 0.03 vs. 0.24 ± 0.01, t = -5.77, P < 0.05; 0.17 ± 0.01 vs. 0.22 ± 0.02, t = -9.18, P < 0.05; and 0.76 ± 0.05 vs. 0.48 ± 0.04, t = -13.12, P < 0.05; F = 77.29, P < 0.001), compared with light injury group.Conclusion: The p-ERK1/2 inhibitor might protect the retina from light-induced photoreceptor degeneration and retinal inflammation.展开更多
Although VEGF-B was discovered as a VEGF-A homolog a long time ago,the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups.Notwithstanding,drugs that inhibit V...Although VEGF-B was discovered as a VEGF-A homolog a long time ago,the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups.Notwithstanding,drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases.It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms.Using comprehensive in vitro and in vivo methods and models,we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed.Mechanistically,we unveil that VEGF-B binds to FGFR1,induces FGFR1/VEGFR1 complex formation,and suppresses FGF2-induced Erk activation,and inhibits FGF2-driven angiogenesis and tumor growth.Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway.Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels,caution is warranted when modulating VEGF-B activity to treat neovascular diseases.展开更多
基金Supported by research grants from the National Key R&D Program of China(No.2017YFC0108200)the Shanghai Committee of Science and Technology(No.16140901000+1 种基金 No.13430710500 No.15DZ1942204)
文摘AIM: To measure the depths of different regions of the anterior chamber(AC) in healthy Chinese adults, and to explore possible correlations with age or gender.METHODS: The AC was imaged by swept-source optical coherence tomography in healthy Chinese adults. The horizontal scan of the right eye was used to measure the anterior chamber depth(ACD) at 199 points.RESULTS: A total of 309 images from 309 subjects were analyzed. The ACD values at nearly all locations were negatively correlated with age(all P<0.05), except for ACD1, 2, 198, and 199(correspond to the iris roots). The mean annual decrease 0.013±0.005 mm/y for all ACDs combined, 0.008±0.004 mm/y for the peripheral region, 0.017±0.003 mm/y for the middle peripheral region, and 0.014±0.001 mm/y for the central region. The mean annual decrease was significantly different among these three regions(P<0.001). The ACD was greater in males than in females(P<0.05). The mean difference in ACD between males and females was 0.081±0.025 mm.CONCLUSION: This study showed that optical coherence tomography can be used to measure the ACD of different regions of the AC. We found reductions in ACD with age, although the reduction varied among different points, in healthy Chinese adults.
文摘AIM: To evaluate the safety, quality and prospects of day-case cataract surgery performed in a Jiangsu public tertiary hospital METHODS: The general and clinical data for patients who underwent day-case cataract surgery between August 1, 2014 and December 31, 2016 at this hospital were collected. The incidences of intraoperative and postoperative complications, preoperative and postoperative bestcorrected visual acuities(BCVAs), delayed discharge rate, rate of unplanned re-admission to hospital, and patient satisfaction were analyzed. RESULTS: A total of 4151 patients received cataract phacoemulsification surgery to correct age-related, congenital, traumatic, or complicated cataracts. Of these, age-related cataracts were the most frequently occurring. Patient age ranged from 18 to 101 y and the vast majority of patients were between 60 and 80 years old. Of the 4151 patients, 64.73%(2687/4151) had a systemic disease. The number of patients increased over the years, with the average number of patients per month being 90.4, 124.83, and 183.42 in 2014, 2015 and 2016, respectively. The average preoperative BCVA was 0.102±0.057 and average postoperative BCVAs at 1 d, 1 wk, and 1 mo post surgery were 0.453±0.264, 0.657±0.285, and 0.734±0.244, respectively. For intraoperative complications, 4.12%(171/4151) had posterior capsule rupture, 0.79%(33/4151) had iris or ciliary body injury, and 0.048%(2/4151) had suprachoroidal hemorrhage. For postoperative complications, 4.38%(182/4151) had cornea edema, 7.78%(323/4151) had intraocular hypertension, 0.096%(4/4151) had IOL toxicity syndrome, 0.28%(12/4151) had retained lens cortex, and 0.048%(2/4151) had hyphema. The delayed discharge rate was 0.82%(44/4151) and the unplanned re-admission to the hospital was 0(0/4151). The patient satisfaction rate was 91.42%(3795/4151). CONCLUSION: Day-case cataract surgery is safe and effective with good prospects for development.
基金Supported by the National Key Research&Development Plan(No.2017YFC0108200)the Shanghai Committee of Science and Technology(No.16140901000+1 种基金 No.13430710500 No.15DZ1942204)
文摘AIM: To investigate changes in the rabbit retina after shortterm and small amounts tamponade of perfluorooctane(PFO).METHODS: New Zealand rabbits were used, and 48 eyes were randomly and evenly assigned into four different groups. The PFO groups received a residue of 0.1 mL of PFO for ophthalmic surgery or 0.1 mL of F-Octane at the end of surgery; eyes from the pars plana vitrectomy(PPV) group were filled with balanced salt solution and those having not received surgical intervention served as controls. Eyes were collected at 1, 4 and 12 wk and studied.RESULTS: Under a microscope, nuclear counts of the inner nuclear layer(INL) and outer nuclear layer(ONL) did not differ among the four groups at all time points; however, slight disarrangement of the ONL and occasional vacuolization of the INL were found in the inferior retina only at 12 wk in two PFO groups. Four of the groups had similar results of Caspase-3 and TNF-α staining at all time points. Alternatively, IL-8 was increased in PFOa and PPV control groups at 4 wk and in all three PPV groups at 12 wk; also, the apoptotic index(%) was similarly increased in all three PPV groups at 4 and 12 wk.CONCLUSION: Both PFOs are well tolerated in rabbit eyes for up to 12 wk, which suggests that they can be used safely as intraoperative tools or for short-term and small amounts tamponade after surgery.
基金Supported by the National Natural Science Foundation for Young Scholar of China(No.81600739)the Shanghai Hospital Development Center(No.SHDC12016116)the Science and Technology Commission of Shanghai Municipality(No.16411953700)
文摘AIM: To investigate the clinical and optical coherence tomography(OCT) features of focal choroidal excavation(FCE) complicated with choroidal neovascularization(CNV) in young and middle aged patients. METHODS: We performed a retrospective review of 26 patients with FCE accompanied by CNV. All patients underwent a complete ophthalmic examination. We analyzed the clinical characteristics of patients, focusing on the spectral-domain OCT features. All patients received intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF) agents. And we assessed the changes of central retinal thickness and best-corrected visual acuity(BCVA) after anti-VEGF therapy. RESULTS: The mean age of 26 patients was 35.5±7.3 y(range, 21-48 y). Of the 26 FCE lesions, 11 were located subfoveal, 6 were parafoveal, and 9 were extrafoveal. The mean FCE depth was 129.8±50.3 μm, and the mean width was 901.3±306.0 μm. The FCE depth was correlated positively with the width, but not correlated with age or refractive error. CNV was located within the excavation(19 eyes) or adjacent to the excavation(7 eyes). After anti-VEGF therapy, the central retinal thickness was significantly reduced and the BCVA was significantly improved. In the absorption process of subretinal fluid, we found that the fluid in the excavations needed to be absorbed at the last. A small amount of residual fluid could still be seen in a few deep excavations even after a longterm follow-up.CONCLUSION: FCE may be an important reason to cause CNV. Especially in young patients with idiopathic CNV, we should pay attention to the use of OCT to check the presence of FCE. Anti-VEGF therapy is generally effective for CNV associated with FCE.
基金grants from the National Natural Science Foundation for Young Scholars of China (No.81400410) National Natural Science Foundation of China (No.81570854).
文摘Background: The demonstrated role of mitogen-activated protein kinase (MAPK) in both cell apoptosis and the inflammation pathway makes it an attractive target for photoreceptor protection. The aim of this study was to investigate the protective effects of MAPK antagonists against photoreceptor degeneration and retinal inflammation in a rat model of light-induced retinal degeneration. Methods:Sprague Dawley rats were treated with intravitreal injections of MAPK antagonists,inhibitors of p-P38,phosphorylated?extracellular regulated kinase (p-ERK) 1/2, and p-c-Jun N-terminal kinase (JNK) just before they were assigned to dark adaptation.After dark adaptation for 24 h, rats were exposed to blue light (2500 lux) in a light box for 24 h, and then returned to the normal 12-h light/12-h dark cycle. Samples were collected at different time points. MAPK expression during light exposure was examined with immunofluorescence. Photoreceptor death was detected with histopathology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of retinal p-ERK1/2, caspase 3, activated caspase 3, tumor necrosis factor (TNF)-α, and interleukin (IL)-1βwas examined by Western blotting. Differences between groups were evaluated using unpaired one-way analysis of variance and least significant difference post hoc tests. Results: MAPKs (P38, ERK1/2, and p-JNK) were phosphorylated and activated in the light injury groups, compared with normal group, and their expressions were mainly elevated in the outer nuclear layer (ONL). Among the selected MAPK antagonists, only the p-ERK1/2 inhibitor attenuated the loss of photoreceptors and the thinning of ONL in light injury groups. Besides, p-ERK1/2 inhibitor refrained light-induced photoreceptor apoptosis, which was presented by TUNELpositive cells. Light injury significantly increased the expression of p-ERK1/2 (1.12 ± 0.06 vs. 0.57 ± 0.08, t = 9.99, P < 0.05; 1.23 ± 0.03 vs. 0.57 ± 0.08, t = 11.90, P < 0.05; and 1.12 ± 0.12 vs. 0.57 ± 0.08, t = 9.86, P < 0.05; F = 49.55, P < 0.001), and induced caspase 3 activating (0.63 ± 0.06 vs. 0.14 ± 0.05, t = 13.67, P < 0.05; 0.74 ± 0.05 vs. 0.14 ± 0.05, t = 16.87, P < 0.05; and 0.80 ± 0.05 vs. 0.14 ± 0.05, t = 18.57, P < 0.05; F = 100.15, P < 0.001), compared with normal group. The p-ERK1/2 inhibitor significantly reduced p-ERK1/2 overexpression (0.61 ± 0.06 vs. 1.12 ± 0.06, t = -9.26, P < 0.05; 0.77 ± 0.06 vs. 1.23 ± 0.03, t = -8.29, P < 0.05; and 0.68 ± 0.03 vs. 1.12 ± 0.12, t = -7.83, P < 0.05; F = 49.55, P < 0.001) and downregulated caspase 3 activating (0.23 ± 0.04 vs. 0.63 ± 0.06, t = -11.24, P < 0.05; 0.43 ± 0.03 vs. 0.74 ± 0.05, t = -8.86, P < 0.05; and 0.58 ± 0.03 vs. 0.80 ± 0.05, t = -6.17, P < 0.05; F = 100.15, P < 0.001), compared with light injury group. No significant change in the total level of caspase 3 was seen in different groups (F = 0.56, P = 0.75). As for inflammation, light injury significantly increased the expression of TNF-α (0.42 ± 0.04 vs. 0.25 ± 0.05, t = 5.99, P < 0.05; 0.65 ± 0.03 vs. 0.25 ± 0.05, t = 14.87, P < 0.05; and 0.86 ± 0.04 vs. 0.25 ± 0.05, t = 22.58, P < 0.05; F = 160.27, P < 0.001) and IL-1β (0.24 ± 0.01 vs. 0.19 ± 0.02, t = 2.33, P < 0.05; 0.35 ± 0.02 vs. 0.19 ± 0.02, t = 7.97, P < 0.05; and 0.48 ± 0.04 vs. 0.19 ± 0.02, t = 14.69, P < 0.05; F = 77.29, P < 0.001), compared with normal group. P-ERK1/2 inhibitor significantly decreased the overexpression of TNF-α (0.22 ± 0.02 vs. 0.42 ± 0.04, t = -7.40, P < 0.05; 0.27 ± 0.02 vs. 0.65 ± 0.03, t = -14.27, P < 0.05; and 0.33 ± 0.03 vs. 0.86 ± 0.04, t = -19.58, P < 0.05; F = 160.27, P < 0.001) and IL?1β (0.13 ± 0.03 vs. 0.24 ± 0.01, t = -5.77, P < 0.05; 0.17 ± 0.01 vs. 0.22 ± 0.02, t = -9.18, P < 0.05; and 0.76 ± 0.05 vs. 0.48 ± 0.04, t = -13.12, P < 0.05; F = 77.29, P < 0.001), compared with light injury group.Conclusion: The p-ERK1/2 inhibitor might protect the retina from light-induced photoreceptor degeneration and retinal inflammation.
基金This study is supported by the State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,and Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science,Guangzhou 510060,P.R.Chinathe National Natural Science Foundation of China(82150710555 and 82220108016 to X.Li,81970823 to Jin Yao and 81830013 to J.O.)+4 种基金a Key Research and Development Plan of Shandong Province(2016GSF201100)the Fundamental Research Funds for the Central Universities(19ykpy151)the long-term structural Methusalem funding by the Flemish Government,Belgiumthe Deutsche Forschungsge-meinschaft(Project No.:394046768-SFB1366)the DZHK partner site Mannheim/Heidelberg to H.F.L.,an ERA PerMed 2020 JTC grant“PROGRESS”.
文摘Although VEGF-B was discovered as a VEGF-A homolog a long time ago,the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups.Notwithstanding,drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases.It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms.Using comprehensive in vitro and in vivo methods and models,we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed.Mechanistically,we unveil that VEGF-B binds to FGFR1,induces FGFR1/VEGFR1 complex formation,and suppresses FGF2-induced Erk activation,and inhibits FGF2-driven angiogenesis and tumor growth.Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway.Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels,caution is warranted when modulating VEGF-B activity to treat neovascular diseases.