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（...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 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-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 8could 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 E2 F2（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.展开更多
文摘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 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-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 8could 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 E2 F2（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.
