Retinal Toxicity of Intravitreal Granulocyte Colony-Stimulating Factor in Rabbit Eyes

ABSTRACT

Purpose: Granulocyte colony-stimulating factor (G-CSF) has potential ocular neuroprotective effects. The aim of this study was to evaluate the retinal toxicity of intravitreal G-CSF in rabbit eye.

Methods: Eight New Zealand albino rabbits, weighing between 2 and 3 kg, were selected for this study. The initial concentration of G-CSF (300 µg/0.5 ml) was titrated to obtain different concentrations of 45 μg, 30 μg, 15 μg, and 7.5 μg in 0.1 ml. Each concentration was injected into two rabbit eyes. For each dose, dextrose was injected in one contralateral eye and the other fellow eye remained non-injected. Electroretinographic (ERG) testing was performed before and 4 weeks after injections. The rabbits were euthanized and the eyes were enucleated 4 weeks after injections and examined using light microscopy and immunohistochemistry.

Results: One rabbit with the injected dosage of 7.5 µg died at the first post-injection day. No sign of intraocular toxicity was found in clinical examination in other rabbits. A significant decrease in at least one of the a- or b-wave measurements of scotopic or photopic responses was found in 45 µg, 15 µg, and 7.5 µg injected eyes. Eyes with an intravitreal injection dosage of 30 µg G-CSF did not have significant changes compared to the baseline values. Histologic and immunohistochemistric studies were unremarkable for pathologic changes in all injected eyes.

Conclusion: While histologic and immunohistochemistric examinations revealed no toxicity in all G-CSF-injected eyes, significant ERG changes were observed in all doses except for the dose of 30 µg/0.1 ml.

KEYWORDS:

• Granulocyte colony-stimulating factor
• intravitreal injection
• toxicity

Acknowledgments

The authors would like to thank Ms. Nadia Sadighi for electrophysiologic examinations and Mr. Alireza Oveisi for anesthetic procedures. None of the authors has any financial interest in the subject matter of this paper.