Histologic studies of the intraocular toxicity of imatinib mesylate in rabbits.
OBJECTIVE
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.
Kitzmann
A S
AS
Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Baratz
K H
KH
Mohney
B G
BG
Pulido
J S
JS
Cameron
J D
JD
Lee
E S
ES
Leof
E B
EB
D000818:Animals; D001549:Benzamides; D004305:Dose-Response Relationship, Drug; D000068877:Imatinib Mesylate; D023421:Models, Animal; D009336:Necrosis / Q000473:pathology; D009900:Optic Nerve / Q000187:drug effects* / Q000473:pathology; D010879:Piperazines / Q000633:toxicity*; D047428:Protein Kinase Inhibitors / Q000633:toxicity*; D011743:Pyrimidines / Q000633:toxicity*; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D014822:Vitreous Body
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate