Deficit of Somatostatin-Like Immunoreactivity in the Vitreous Fluid of Diabetic Patients

Abstract

OBJECTIVE -To evaluate the vitreous levels of somatostatin-like immunoreactivity (SLI) in patients with proliferative diabetic retinopathy (PDR). RESEARCH DESIGN AND METHODS-A total of 14 diabetic patients with PDR, in whom a vitrectomy was performed, were included in the study. Sixteen nondiabetic patients, with other conditions requiring vitrectomy, served as a control group. Both venous blood and vitreous samples were collected at the time of vitreoretinal surgery. Patients in whom intravitreous hemoglobin was detectable were excluded. In addition, a correction for plasma levels of SLI and intravitreal proteins was performed. SLI was measured by radioimmunoassay and vitreous hemoglobin by spectrophotometry.RESULTS -SLI in the vitreous fluid was significantly lower in diabetic patients than in the control group (68 Ϯ 18.7 vs. 193.6 Ϯ 30.8 pg/ml, P Ͻ 0.01). The vitreous SLI-to-plasma SLI ratio was strikingly higher in nondiabetic subjects than in diabetic patients with PDR (5.3 [1.2-71.1] vs. 0.6 [0.03-4.1], P Ͻ 0.01). After correcting for total vitreous protein concentration, SLI (pg/mg of proteins) remained significantly higher in nondiabetic control subjects than in diabetic patients with , P Ͻ 0.0001). Remarkably, intravitreous levels of SLI were higher than those obtained in plasma in nondiabetic control subjects (193.6 Ϯ 30.8 vs. 43.5 Ϯ 10.7 pg/ml, P Ͻ 0.0001). Finally, a lack of relationship between plasma and vitreous levels of SLI was observed in both diabetic patients with PDR and nondiabetic control subjects.CONCLUSIONS -The significantly higher SLI in the vitreous fluid than in plasma detected in nondiabetic control subjects supports the concept that somatostatin plays a relevant role in retinal homeostasis. In addition, the intravitreous deficit of SLI observed in diabetic patients with PDR suggests that it might contribute to the process of retinal neovascularization. Diabetes Care 25:2282-2286, 2002S omatostatin is a peptide that was originally identified as the hypothalamic factor responsible for inhibition of the release of growth hormone (GH) from the anterior pituitary (1). Subsequent studies have shown that somatostatin has a much broader spectrum of inhibitory actions and that it is much more widely distributed in the body, occurring not only in many regions of the central nervous system but also in many tissues of the digestive tract, including the stomach, intestine, and pancreas (2). Somatostatin-14 and -28 are the two principal bioactive products cleaved from the COOH-terminus of prosomatostatin in different cells and the main circulating forms of somatostatin (2,3). Somatostatin-13, converted from somatostatin-14 by the action of tissue aminopeptidases, is also present in plasma as prosomatostatin, and collectively all of these peptides contribute to the measurement of somatostatin-like immunoreactivity (SLI) (3). Somatostatin mediates its multiple biologic effects via specific plasma membrane receptors that belong to the family of G-protein-coupled receptors having seven transmembrane...

Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy

“…Second, the disruption of the bloodretina barrier that occurs in diabetic retinopathy produces an increase in proteins in the vitreous body of diabetic patients. Indeed, we have repeatedly detected three-to fourfold higher levels of intravitreal proteins in diabetic patients than in non-diabetic subjects [2][3][4]. Therefore, an elevated intravitreal level of a particular protein does not necessarily indicate an increase in intraocular production, and might simply reflect a non-specific increase in protein levels due to serum diffusion.…”

Neurodegeneration: An early event of diabetic retinopathy

“…Therefore, RPE rather than neuroretina is the main source of SST, at least in humans. The amount of SST produced by the human retina is significant as deduced by the strikingly high levels found in the vitreous fluid [44,45] . Apart from SST, SSTRs are also expressed in the retina, with SSTR1 and SSTR2 being the most widely expressed [43,46,47] .…”

Lower Somatostatin Expression Is an Early Event in Diabetic Retinopathy and Is Associated With Retinal Neurodegeneration

“…In recent years, we have demonstrated higher levels of SST in the vitreous fluid than in plasma in nondiabetic subjects, and a significantly lower intravitreous concentration of SST was detected in both proliferative diabetic retinopathy (PDR) (9) and diabetic macular edema (DME) patients (10) than in nondiabetic control subjects; SST-28 was the main molecular variant accounting for this deficit (11). Although vitreous fluid analysis can be used as a surrogate for events in the retina, studies to evaluate SST expression in the retina in diabetic patients are needed.…”