Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy
AIM: To confirm the role of angiopoietin-like protein 8 (Angptl 8) in proliferative diabetic retinopathy (PDR). METHODS: The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy (NDR) patients (idiopathic macular hole patients) were collected and the expression of Angptl 8 was...
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Press of International Journal of Ophthalmology (IJO PRESS)
2017-12-01
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Online Access: | http://www.ijo.cn/en_publish/2017/12/20171205.pdf |
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author | Chang-Xia Dong Cai-Ping Song Chun-Ping Zhang Mei Dong Xiu-Rong Gong He-Ying Gao Hong Wang |
author_facet | Chang-Xia Dong Cai-Ping Song Chun-Ping Zhang Mei Dong Xiu-Rong Gong He-Ying Gao Hong Wang |
author_sort | Chang-Xia Dong |
collection | DOAJ |
description | AIM: To confirm the role of angiopoietin-like protein 8 (Angptl 8) in proliferative diabetic retinopathy (PDR).
METHODS: The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy (NDR) patients (idiopathic macular hole patients) were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay (ELISA). Experimental diabetes mice model was induced with streptozotocin. The expression of glycosylated hemoglobin and Angptl 8 in sera was detected. Recombinant Angptl 8 was re-infused into wild type (WT) diabetic mice and spatial frequency threshold and contrast sensitivity were measured. In vitro retinal pigment epithelium (RPE) were stimulated by recombinant Angptl 8 for 24h. MMT assay were used to detect cell proliferation. At the same time, qRT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells.
RESULTS: The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients (F=99.02, P<0.0001 in sera; t=10.42, P<0.0001 in aqueous). After successfully establishing the diabetic mice model, we found that glycosylated hemoglobin and Angptl 8 expression levels were increased. Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity (P<0.01). In vitro, RPE cells stimulated by recombinant Angptl 8 could increase the relative absorbance of MMT assay (1.486±0.042 vs 1.000±0.104, P<0.05) and proliferating cell nuclear antigen (PCNA) expression (0.55±0.01 vs 0.29±0.03, P<0.05). The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1 (4.973±0.205 vs 2.720±0.197, P<0.05), cyclin F (5.690±0.219 vs 4.297±0.292, P<0.05) and E2F2 (2.297±0.102 vs 1.750±0.146, P<0.05), and reducing the expression of proliferation-inhibiting factors cdkn1 (2.370±0.074 vs 3.317±0.135, P<0.05) and cdkn2 (4.793±0.065 vs 5.387±0.149, P<0.05).
CONCLUSION: The expression of Angptl 8 is increased in PDR, and the increased Angptl 8 can promote proliferation and increase proliferation-related factors. |
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spelling | doaj.art-15ffcb9286db436a927d277500ab015c2022-12-22T03:22:59ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982017-12-0110121819182310.18240/ijo.2017.12.05Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathyChang-Xia Dong0Cai-Ping Song1Chun-Ping Zhang2Mei Dong3Xiu-Rong Gong4He-Ying Gao5Hong Wang6Department of Ophthalmology, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, ChinaDepartment of Ophthalmology, Weihai Municipal Hospital, Weihai 264200, Shandong Province, ChinaDepartment of Stomatology, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, ChinaDepartment of Ophthalmology, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, ChinaDepartment of Ophthalmology, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, ChinaDepartment of Ophthalmology, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, ChinaDepartment of Ophthalmology, Shandong Qilu Hospital, Shandong University, Jinan 25000, Shandong Province, ChinaAIM: To confirm the role of angiopoietin-like protein 8 (Angptl 8) in proliferative diabetic retinopathy (PDR). METHODS: The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy (NDR) patients (idiopathic macular hole patients) were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay (ELISA). Experimental diabetes mice model was induced with streptozotocin. The expression of glycosylated hemoglobin and Angptl 8 in sera was detected. Recombinant Angptl 8 was re-infused into wild type (WT) diabetic mice and spatial frequency threshold and contrast sensitivity were measured. In vitro retinal pigment epithelium (RPE) were stimulated by recombinant Angptl 8 for 24h. MMT assay were used to detect cell proliferation. At the same time, qRT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells. RESULTS: The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients (F=99.02, P<0.0001 in sera; t=10.42, P<0.0001 in aqueous). After successfully establishing the diabetic mice model, we found that glycosylated hemoglobin and Angptl 8 expression levels were increased. Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity (P<0.01). In vitro, RPE cells stimulated by recombinant Angptl 8 could increase the relative absorbance of MMT assay (1.486±0.042 vs 1.000±0.104, P<0.05) and proliferating cell nuclear antigen (PCNA) expression (0.55±0.01 vs 0.29±0.03, P<0.05). The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1 (4.973±0.205 vs 2.720±0.197, P<0.05), cyclin F (5.690±0.219 vs 4.297±0.292, P<0.05) and E2F2 (2.297±0.102 vs 1.750±0.146, P<0.05), and reducing the expression of proliferation-inhibiting factors cdkn1 (2.370±0.074 vs 3.317±0.135, P<0.05) and cdkn2 (4.793±0.065 vs 5.387±0.149, P<0.05). CONCLUSION: The expression of Angptl 8 is increased in PDR, and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.http://www.ijo.cn/en_publish/2017/12/20171205.pdf1823angiopoietin-like protein 8proliferative diabetic retinopathyretinal pigment epitheliumproliferation |
spellingShingle | Chang-Xia Dong Cai-Ping Song Chun-Ping Zhang Mei Dong Xiu-Rong Gong He-Ying Gao Hong Wang Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy International Journal of Ophthalmology 1823 angiopoietin-like protein 8 proliferative diabetic retinopathy retinal pigment epithelium proliferation |
title | Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy |
title_full | Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy |
title_fullStr | Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy |
title_full_unstemmed | Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy |
title_short | Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy |
title_sort | clinical and experimental study on angiopoietin like protein 8 associated with proliferative diabetic retinopathy |
topic | 1823 angiopoietin-like protein 8 proliferative diabetic retinopathy retinal pigment epithelium proliferation |
url | http://www.ijo.cn/en_publish/2017/12/20171205.pdf |
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