Octreotide, a Somatostatin Analogue, Fails to Inhibit Hypoxia-induced Retinal Neovascularization in the Neonatal Rat

Author:

Averbukh Edward1,Halpert Michael1,Yanko Ravit2,Yanko Lutza1,Peèr Jacob1,Levinger Samuel1,Flyvbjerg Allan3,Raz Itamar12

Affiliation:

1. Departments of Ophthalmology, Hadassah University Hospital, P. O. Box 12000, Jerusalem 91120, Israel

2. Internal Medicine, Hadassah University Hospital, Jerusalem, Israel

3. Department of Diabetes and Endocrinology, Institute of Experimental Clinical Research, Aarhus Kommunehospital, Denmark

Abstract

Objective:Octreotide, a somatostatin analogue, has been shown to prevent angiogenesis in diversein vitromodels. We evaluated its effect on retinal neovascularizationin vivo, using a neonatal rat retinopathy model.Methods:We used, on alternating days, hypoxia (10%O2) and hyperoxia (50%O2) during the first 14 days of neonatal rats, to induce retinal neovascularization. Half of the rats were injected subcutaneously with octreotide 0.7 μg/g BW twice daily. At day 18 the eyes were evaluated for the presence of epiretinal and vitreal hemorrhage, neovascularization and epiretinal proliferation. Octreotide pharmacokinetics and its effect on serum growth hormone (GH) and insulin-like growth factor I (IGF-I) were examined in 28 rats.Results:Serum octreotide levels were 667 μg/1 two hours after injection, 26.4 μg/1 after nine hours and 3.2 μg/1 after 14 hours. GH levels were decreased by 40% (p= 0.002) two hours after injection but thereafter returned to baseline. IGF-I levels were unchanged two hours after injection and were elevated by 26% 14 hours after injection (p= 0.02). Epiretinal membranes were highly associated with epiretinal hemorrhages (p< 0.001), while retinal neovascularization was notably associated with vitreal hemorrhages (p< 0.001).Conclusions:Twice-daily injections of octreotide failed to produce sustained decrease in serum GH, but produced rebound elevation of serum IGF-I. Accordingly, no statistically significant effect of injections on retinal pathology was noted. This finding, however, does not contradict our assumption that GH suppression may decrease the severity of retinopathy.

Publisher

Hindawi Limited

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism

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