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Ocular toxicity of intravitreous transforming growth factor-beta 1
C Liang1, G A Peyman, J Federman
1LSU Eye Center, Louisiana State University Medical Center, School of Medicine, New Orleans 70112-2234, USA.
Purpose:
To evaluate the ocular toxicity of intravitreous transforming growth factor-beta 1 (TGF-beta(1)).
Methods:
Eyes of New Zealand white rabbits were injected intravitreally with TGF-beta(1) in doses of 20, 10, 5, 1 or 0.5 micrograms. 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 micrograms TGF-beta(1) or nothing, were checked 5 days after injection.
Results:
Corneal opacity was caused by doses > or = 10 micrograms in 7 of 7 eyes; by doses of 5 micrograms in 3 of 4 eyes; and by doses of 1 microgram in 1 of 4 eyes. Doses > or = 5 micrograms 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 micrograms TGF-beta(1), 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 micrograms TGF-beta(1) was twice that of the normal cornea and some corneal endothelial cells lost their hexagonal shape.
Conclusion:
TGF-beta(1) injected intravitreally at doses > or = 1 micrograms is toxic to the cornea. Retinal function is only slightly disturbed by 20 micrograms of TGF-beta(1).
Insights
Intravitreous transforming growth factor-beta 1 (TGF-beta(1)) at doses of 1 microgram or higher causes corneal toxicity in rabbits. Retinal function was minimally affected by TGF-beta(1) ocular toxicity.
Area of Science:
- Ophthalmology
- Toxicology
- Cell Biology
Background:
- Transforming growth factor-beta 1 (TGF-beta(1)) is a cytokine with diverse biological functions.
- Understanding the ocular toxicity of TGF-beta(1) is crucial for its therapeutic applications and safety assessments.
Purpose of the Study:
- To evaluate the ocular toxicity of intravitreous transforming growth factor-beta 1 (TGF-beta(1)).
Main Methods:
- New Zealand white rabbits received intravitreous injections of varying doses of TGF-beta(1).
- Ocular assessments included electroretinography, clinical examination, and histological analysis.
- Corneal endothelium was examined in fresh corneas post-injection.
Main Results:
- TGF-beta(1) doses >= 1 microgram induced corneal opacity and pannus formation.
- Corneal thickness doubled and endothelial cell morphology was altered at 20 micrograms.
- Electroretinography showed transient B-wave amplitude reduction, with recovery except at the highest dose.
Conclusions:
- Intravitreous TGF-beta(1) at doses >= 1 microgram is toxic to the cornea.
- Retinal function is only slightly disturbed by high-dose TGF-beta(1) administration.