Systemic levels contribute significantly to increased intraocular IGF-I, IGF-II and IGF-BP3 in proliferative diabetic retinopathy

Increased intraocular levels of angiogenic growth factors such as insulin-l ike growth factor I (IGF-I) have been demonstrated in proliferative diabeti c retinopathy (PDR). It is unclear whether increased leakage of the blood r etina barrier or local synthesis primarily determine intraocular levels of IGFs in man, which is of special interest regarding possible therapeutic op tions with somatostatin analogues in PDR. This is the first study investiga ting parallely serum and vitreous levels of IGF-I/II, IGF-BP3 and the liver -derived permeability marker albumin to determine in vivo the amount of cir culation-derived intraocular IGFs. A control group without retinal prolifer ation and patients with PDR were compared. Levels of IGF-I/II, IGF-BP3 and albumin were determined by immunological methods. Vitreous levels of albumi n were 2.2-fold elevated in patients with PDR (254.1 +/- 37.2 mg/dl; n = 27 ; p = 0.0027) compared to controls (115.7 +/- 36.2 mg/dl; n = 10), whereas serum levels were slightly decreased in diabetes patients (5049 +/- 196 mg/ dl vs. 4330 +/- 186 mg/dl; p = 0.0283). This was comparable to an increase of IGF-I/II and IGF-BP3 in vitreous from PDR patients (IGF-I: 2.3 +/- 1.1 n g/ml; p = 0.005. IGF-II: 37.9 +/- 4.9 ng/ml; p = 0.0003. IGF-BP3: 97.9 +/- 26.9 ng/ml; p = 0.0001; n = 34) compared to controls (IC;F-I: 0.7 +/- 0.1 n g/ml. IGF-II: 21.3 +/- 4.2 ng/ml. IGF-BP3: 31.3 +/- 4.9 ng/ml; n = 19). Ser um levels did not differ significantly among the groups regarding IGF-I, II and IGF-BP3. Intraocular albumin and IGF-I levels calculated as percentage of the respective serum levels correlated significantly (r = 0.42; p = 0.0 12). This study demonstrates that influx of IGF-I, II and IGF-BP3 in PDR qu antitatively parallels influx of the liver derived serum protein albumin su ggesting that leakage of the blood retina barrier and serum levels of IGF p rimarily determine intravitreal IGF levels rather than local synthesis. Sup pression of systemic IGF levels by new, highly effective somatostatin-analo gues therefore provides a promising approach to prevent PDR.