Somatostatin Molecular Variants in the Vitreous Fluid

Abstract

OBJECTIVE -There is growing evidence to indicate that somatostatin could be added to the list of natural antiangiogenic factors that exist in the vitreous fluid. In addition, a deficit of intravitreous somatostatin-like immunoreactivity (SLI) has been found in diabetic patients with proliferative diabetic retinopathy (PDR). In the present study, we have determined the main molecular variants of somatostatin (somatostatin-14 and somatostatin-28) in the vitreous fluid and plasma of nondiabetic control subjects and diabetic patients with PDR. In addition, the contribution of cortistatin, a neuropeptide with strong structural similarities to somatostatin, to SLI and its levels in vitreous and plasma in both nondiabetic and diabetic patients has also been measured. RESERCH DESIGN AND METHODS-Plasma and vitreous fluid from 22 diabetic patients with PDR and 22 nondiabetic control subjects were analyzed. Somatostatin-14, somatostatin-28 and cortistatin were measured by radioimmunoassay but separation by highperformance liquid chromatography was required to measure somatostatin-14.RESULTS -The predominant molecular form of somatostatin within the vitreous fluid was somatostatin-28 (fivefold higher than somatostatin-14 in control subjects and threefold higher in patients with PDR). Cortistatin significantly contributed to SLI and its intravitreous levels were higher than those detected in plasma (nondiabetic control subjects: 147 vs. 78 [24 -32] pg/ml; patients with PDR: 187 vs. 62 [24 -472] pg/ml; P ϭ 0.01 for both). Intravitreous somatostatin-14 was similar in both subjects with PDR and the control group (P ϭ 0.87). By contrast, somatostatin-28 concentration was lower in patients with PDR than in nondiabetic control subjects (350 Ϯ 32 vs. 595 Ϯ 66 pg/ml; P ϭ 0.004).CONCLUSIONS -Somatostatin-28 is the main molecular variant in the vitreous fluid. The intravitreous SLI deficit detected in patients with PDR is mainly due to somatostatin-28. Cortistatin is abundant in the vitreous fluid and significantly contributes to SLI. These findings could open up new strategies for PDR treatment. Diabetes Care 28:1941-1947, 2005P roliferative diabetic retinopathy (PDR) represents a highly prevalent cause of visual loss in western countries and is the leading cause of new-onset blindness among people of working age (1). There is now ample evidence to suggest that the development of diabetic retinopathy is a multifactorial process in which it is not just the angiogenic factors alone but the balance between angiogenic and antiangiogenic factors that is crucial. Inhibition of angiogenesis has therefore become a target for the treatment of retinal neovascularization.Several pilot studies using the somatostatin analog octreotide in patients with early proliferative and severe non-PDR have revealed decreased incidence of progression into proliferative retinopathy needing panretinal laser treatment (2,3). In addition, the incidence of vitreous hemorrhage and the need for vitreoretinal surgery was also significantly reduced in octreotide-tr...

Physiology and pathology of somatostatin in the mammalian retina: A current view

“…SRIF levels in the vitreous of patients with diabetic retinopathy are significantly lower than those in nondiabetic control subjects (Hernandez et al, 2005;Simo et al, 2002). This observation suggests that the intravitreous deficit of SRIF may contribute to the process of retinal neovascularisation typical of proliferative retinopathy and supports the concept that adequate levels of SRIF are needed for the maintenance of retinal homeostasis.…”

Diabetic retinopathy: A comprehensive review

“…[81] A multicenter, randomized, placebo-controlled clinical trial of octreotide is currently under way in patients with severe NPDR and early PDR. [82] Place of other pharmacotherapies in the management of DR Results of clinical trials do not support the use of anti-platelet agents, [83] aldose reductase inhibitors [84] and advanced glycation endproducts inhibitors [85] in the management of DR. The role of COX-2 inhibitor, celecoxib, in the treatment of PDR is being evaluated in an ongoing clinical trial.…”

Vitreous levels of erythropoietin in patients with macular oedema secondary to retinal vein occlusions: a comparative study with diabetic macular oedema

“…We found lower concentrations of somatostatin (SST), an antiangiogenic factor, in the vitreous fluid of patients with proliferative diabetic retinopathy as compared with controls, suggesting that SST deficit can contribute to neovascularization in this disease. 8,9 In addition, SST levels are decreased in the vitreous fluid of patients with diabetic macular oedema (DME), which suggests a relationship between vascular permeability and SST deficit. 10 Erythropoietin (EPO) is a glycoprotein with a well recognized erythropoietic function.…”