Vitreous levels of IGF-I, IGF binding protein 1, and IGF binding protein 3 in proliferative diabetic retinopathy: a case-control study.

Abstract

OBJECTIVE: To evaluate vitreous levels of IGF-I and its binding proteins IGFBP-1 and IGFBP-3 in patients with proliferative diabetic retinopathy (PDR). Because intravitreal proteins are elevated in patients with PDR due to the disruption of the blood-retinal barrier, we have corrected vitreal IGF-I and IGFBPs by total vitreal proteins to avoid this confounding factor. RESEARCH DESIGN AND METHODS: We compared 21 diabetic patients with proliferative retinopathy (group A) and 13 nondiabetic patients (group B) in whom a vitrectomy was performed. Both groups were matched by age, serum IGF-I, IGFBP-1, and IGFBP-3 levels. Serum and vitreous levels of IGF-I, IGFBP-1, and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by turbidimetric method. RESULTS: Vitreal levels of IGF-I were elevated in group A (median 1.35 ng/ml [range 0.3-8.7]) in comparison with group B (median 0.25 ng/ml [range 0-1.38]), P<0.001. After adjusting by vitreal proteins [ratio IGF-I (ng/ml)/protein (mg/ml)], the differences remain significant (P<0.005). Vitreal levels of IGFBP-1 and IGFBP-3 were also elevated in diabetic patients (IGFBP-1: group A, median 1.6 ng/ml [range 0.6-20.7]; group B, median 0.4 ng/ml [range 0.3-1.9], P<0.001. IGFBP-3: group A, median 102.6 ng/ml [range 53.9-350.8]; group B, median 29.0 ng/ml [range 3.2-87.8], P<0.001). However, when the ratio IGFBP/protein was considered, the differences were not significant. CONCLUSIONS: Intraocular synthesis contributes to elevated vitreous concentrations of IGF-I found in PDR. By contrast, unspecific increase of intravitreal proteins is the main factor explaining the elevated vitreous levels of IGFBP-1 and IGFBP-3 found in diabetic patients.

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.…”

“…The exclusion criteria were as follows: (1) previous vitreoretinal surgery; (2) photocoagulation in the preceding 6 months; (3) recent vitreous haemorrhage (<3 months before vitrectomy) or intravitreous haemoglobin >5 mg/ml; (4) renal failure (creatinine ≥120 μmol/l); and (5) other chronic diseases apart from diabetes. Details of vitrectomy and sample collection have been described previously elsewhere [3].…”

Insulin-Like Growth Factor-I Plays a Pathogenetic Role in Diabetic Retinopathy

“…Several studies have indicated an association between IGF-I levels and progression of diabetic retinopathy. [47][48][49] Exogenous IGF-I, as part of IGF-I replacement therapy, can have detrimental effects in the retinal circulation of humans and can cause blood-retinal barrier breakdown. 27 However, direct causal evidence regarding the role of IGF-I in diabetic retinopathy, beyond the above-mentioned associations, was still lacking.…”

The pathogenesis of diabetic retinopathy: old concepts and new questions

“…213 IGFBPs 1, 2 and 3 have been reported to be significantly increased in vitreous from patients with PDR but not in nonischaemic eye disease. [214][215][216] The contribution of leakage of the blood retinal barrier and local synthesis to vitreous levels of these proteins is unclear, however, local synthesis will certainly contribute. Comparison of cultured retinal endothelial cells from normal and diabetic donors demonstrates a decrease in IGF-1 and an increase in the IGFBP 1, 2 and 5 message for diabetic cultures compared to normals.…”