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


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 measured separately in neuroretina and retinal pigment epithelium (RPE). In addition, SST-28 (radioimmunoassay) was measured in the vitreous fluid. Glial fibrillar acidic protein (GFAP) was assessed by immunofluorescence 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 immunoreactivity 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.
Carrasco
Esther
E
Diabetes Research Unit, Institut de Recerca Hospital Universitari Vall d'Hebron, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Hernández
Cristina
C
Miralles
Adela
A
Huguet
Pere
P
Farrés
Jaume
J
Simó
Rafael
R
D003930:Diabetic Retinopathy / Q000235:genetics*; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D009410:Nerve Degeneration / Q000235:genetics; D009900:Optic Nerve / Q000473:pathology*; D010857:Pigment Epithelium of Eye / Q000473:pathology / Q000503:physiopathology; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000235:genetics*; D013004:Somatostatin / Q000235:genetics*
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D013004:Somatostatin