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Updated: Jul 7, 2026
Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
Published on: July 23, 2016
Histologic studies of the intraocular toxicity of imatinib mesylate in rabbits
A S Kitzmann1, K H Baratz, B G Mohney
1Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Purpose:
To evaluate histologic signs of toxicity of the protein tyrosine kinase inhibitor, imatinib mesylate, in rabbit eyes.
Methods:
Twenty Dutch-belted rabbits underwent intravitreal injections of 0.1 ml solutions of imatinib mesylate. Ten rabbits were killed and enucleated 1 week after injection of imatinib mesylate (1.65 mg (four eyes), 165 microg (four eyes), and 16.5 microg (two eyes)). Ten rabbits injected with imatinib mesylate (165 microg (five eyes) and 825 microg (five eyes)) were enucleated 1 month later. Eyes were fixed in 10% formalin and stained with haematoxylin and eosin for microscopic examination.
Results:
All four eyes injected with 1.65 mg of imatinib mesylate and enucleated at 1 week demonstrated ocular toxicity. All four eyes injected with 165 microg and enucleated at 1 week showed no ocular toxicity. One of the two eyes injected with 16.5 microg and enucleated at 1 week revealed focal areas of subretinal fluid and retinal undulations, suggestive of retinal oedema. None of the 10 eyes injected with imatinib mesylate at either the 165 or 825 microg dose and enucleated at 1 month showed ocular toxicity.
Conclusions:
Imatinib mesylate at 1.65 mg caused extensive retinal toxicity in rabbit eyes. In contrast, lower doses did not appear to cause toxicity, but may be associated with retinal oedema.
Insights
High-dose imatinib mesylate (1.65 mg) caused significant retinal toxicity in rabbit eyes. Lower doses showed no toxicity but may be linked to retinal edema, indicating a dose-dependent effect of this protein tyrosine kinase inhibitor.
Area of Science:
- Ophthalmology
- Pharmacology
- Toxicology
Background:
- Imatinib mesylate is a protein tyrosine kinase inhibitor used in cancer therapy.
- Understanding its ocular toxicity is crucial for patient safety.
Purpose of the Study:
- To evaluate the histologic signs of ocular toxicity of imatinib mesylate in a rabbit model.
- To determine the dose-dependent toxicity of intravitreally administered imatinib mesylate.
Main Methods:
- Dutch-belted rabbits received intravitreal injections of imatinib mesylate at varying doses (16.5 microg to 1.65 mg).
- Eyes were enucleated 1 week and 1 month post-injection for histological examination.
- Standard hematoxylin and eosin staining was used for microscopic analysis.
Main Results:
- The highest dose (1.65 mg) resulted in extensive ocular toxicity in all treated eyes.
- Lower doses (165 microg and 825 microg) showed no toxicity at both 1-week and 1-month follow-ups.
- One eye at 16.5 microg exhibited signs suggestive of retinal edema.
Conclusions:
- A high dose of imatinib mesylate (1.65 mg) is toxic to rabbit retina.
- Lower doses of imatinib mesylate appear safe for ocular tissues.
- Potential for retinal edema at lower doses warrants further investigation.
