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B. J. Song, H. Cai, S. Chang, J. C. Tsai, M. Forbes, L. V. Del Priore; Intravitreal Injection of Recombinant Human Erythropoietin: A Study of Retinal Toxicity Using Electroretinography and Fluorescein Angiography in Rabbits. Invest. Ophthalmol. Vis. Sci. 2007;48(13):251.
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Recombinant human erythropoietin (rhEPO) is an approved drug for the treatment of chronic anemia. In addition to its hematopoietic benefits, rhEPO has recently been shown to have a therapeutic effect in various animal models of glaucoma and retinal degeneration. However, the effects of intravitreal rhEPO have yet to be studied in a non-rodent model. The purpose of this study is to evaluate the safety and potential side effects of varying doses of a single intravitreal injection of rhEPO in rabbits.
Fourteen New Zealand rabbits were randomly divided into one of 6 groups: control (no injection), vehicle injection, and rhEPO injections of 100 U, 250 U, 500 U, and 1000 U (N = 2-4 rabbits per group). Only the right eye of each animal was injected. Retinal function was assessed by electroretinography (ERG) on both eyes simultaneously using a Ganzfeld dome at baseline (one day before injection), and then 3, 7, 14, and 21 days post-injection. After one hour of dark-adaptation, scotopic responses were elicited using a stimulus of 0.1 cd-s/m2 on a dark background. Photopic responses were measured with a stimulus of 3.0 cd-s/m2 on a white background of 30 cd/m2 following 5 minutes of light adaptation. Intraocular pressure (IOP) was recorded after each ERG using a Tonopen XL. On post-injection day 28, fluorescein angiography (FA) was performed. Angiograms were graded for neovascularization from 0 to +4, where 0 represented the absence of vascular abnormalities and +4 represented neovascularization with identifiable capillary loops involving the optic disk and medullary rays. Statistical analysis was carried out using two-way ANOVA.
Between all groups and time points, there were no statistically significant differences in scotopic or photopic a- or b-wave amplitudes or implicit times on ERG (except for scotopic b-wave amplitude of the rhEPO 500 U group on day 21). FA showed no evidence of neovascularization or fluorescein leakage during the early or late phase in any group. All rabbits received a neovascularization grade of 0. Differences in IOP were not statistically significant between groups or time points (p>0.05).
A single 0.1 ml intravitreal injection of rhEPO at a dose of up to 1000 U does not appear to cause adverse effects on retinal vasculature, IOP, or retinal function as assessed by ERG. Further studies are needed to investigate the safety and efficacy of rhEPO as a candidate treatment agent for neurodegenerative diseases of the eye.
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