Lower Somatostatin expression is an early event in diabetic retinopathy and is associated with retinal neurodegeneration

被引:159
作者
Carrasco, Esther
Hernandez, Cristina
Miralles, Adela
Huglet, Pere
Farrés, Jaunie
Simo, Rafael
机构
[1] Hosp Univ Vall Dhebron, Inst Recerca, Diabet Res Unit, Barcelona 08035, Spain
[2] Tissue Bank & Cell Therapy Ctr, Barcelona, Spain
[3] Univ Autonoma Barcelona, Hosp Univ Vall Dhebron, E-08193 Barcelona, Spain
关键词
D O I
10.2337/dc07-0332
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE - To test the hypothesis that a reduction of somatostatin (SST) in the retina exists in patients without clinically detectable diabetic retinopathy and that it is associated with retinal neurodegeneration. RESEARCH DESIGN AND METHODS - Human diabetic postmortem eyes (n = 10) without clinically detectable retinopathy were compared with eyes (n = 10) from nondiabetic donors. SST mRNA (RT-PCR) and SST-28 immunoreactivity (confocal laser) were measure separately in neuroretina and retinal pigment epithelium WE). In addition, SST-28 (radioimmunoassay) was measured in the vitreous fluid. Glial fibrillar acidic protein (GFAP) was assessed by immuno fluorescence and Western blot. Apoptotic cells were quantified using transferase-mediated dUTP nick-end labeling. RESULTS - A higher expression of SST was detected in RPE than neuroretina in both groups. SST mRNA levels and SST-28 immmoreactivity were significantly lower in both RPE and the neuroretina from diabetic donors compared with nondiabetic donors. These results were in agreement with those obtained by measuring SST-28 in the vitreous fluid of the same donors. Increased GFAP and a higher degree of apoptosis were observed in diabetic retinas compared with nondiabetic retinas. These changes were most evident in patients with the higher deficit of SST. CONCLUSIONS - Underproduction of SST is an early event in the eyes of diabetic patients and is associated with glial activation and neural death. in addition, our results suggest that RPE is an important source of SST in the human eye. The possible role of the lower production of SST in the pathogenesis of diabetic retinopathy requires further investigation.
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页码:2902 / 2908
页数:7
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