Chang-Xia Dong1, Cai-Ping Song2, Chun-Ping Zhang3, Mei Dong1, Xiu-Rong Gong1, He-Ying Gao1, Hong Wang4. 1. Department of Ophthalmology, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, China. 2. Department of Ophthalmology, Weihai Municipal Hospital, Weihai 264200, Shandong Province, China. 3. Department of Stomatology, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, China. 4. Department of Ophthalmology, Shandong Qilu Hospital, Shandong University, Jinan 25000, Shandong Province, China.
Abstract
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.
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 diabetesmice 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) diabeticmice 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 diabeticmice model, we found that glycosylated hemoglobin and Angptl 8 expression levels were increased. Re-infusion of recombinant Angptl 8 into WT diabeticmice 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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