Ocular toxicity of intravitreous transforming growth factor-beta 1

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Abstract
Purpose: To evaluate the ocular toxidty of intravitreous transforming growth factor-beta 1 (TGF-β1). Methods: Eyes of New Zealand white rabbits were injected intravitreally with TGF-β1 in doses of 20,10, 5, 1 or 0.5 µg. Electroretinography and clinical examination were performed before and after the injection. At either 10 or 30 days after injection, the eyes were enucleated and examined histologically. The endothelium of fresh corneas, which had received 20 µg TGF-β or nothing, were checked 5 days after injection. Results: Corneal opacity was caused by doses ≥10 µg in 7 of 7 eyes; by doses of 5 µg in 3 of 4 eyes; and by doses of 1 µg in 1 of 4 eyes. Doses ≥ 5 µg also caused pannus formation in 15 of 16 eyes. Ten days after injection there was some decrease in B-wave amplitude on electroretinography. Thirty days after injection the electroretinographic responses had recovered, except in the eyes injected with 20 µg TGF-β1, which still showed a decrease in step 1. Histological examination of paraffin sections did not demonstrate significant change. Corneal thickness of the eyes receiving 20 µg TGF-β1 was twice that of the normal cornea and some corneal endothelial cells lost their hexagonal shape. Conclusion: TGF-β1 injected intravitreally at doses ≥1 µg is toxic to the cornea. Retinal function is only slightly disturbed by 20 µg of TGF β1.