Evaluation of a commercial recombinant tissue-type plasminogen activator preparation in the subretinal space of the cat.
To explore the feasibility of using human recombinant tissue-type plasminogen activator in the management of subretinal hemorrhage, we examined the toxic effects of a commercial preparation of human recombinant tissue-type plasminogen activator in the subretinal space of the holangiotic retina of the cat. Various concentrations of human recombinant tissue-type plasminogen activator and controls were infused into the subretinal space with a glass micropipette (40- to 60-microns tip) to form a retinal bleb. Concentrations from 2.5 mg/L to 200 mg/L were well tolerated without ultrastructural toxic effects, while 1000 mg/L of human recombinant tissue-type plasminogen activator caused severe, irreversible toxic effects to the photoreceptor-retinal pigment epithelium complex. This toxic effect appeared to be due to the carrier vehicle rather than the human recombinant tissue-type plasminogen activator protein itself. Our results demonstrate that commercially prepared human recombinant tissue-type plasminogen activator can be safely used in the subretinal space of the cat with the range necessary for fibrinolysis.
Benner
J D
JD
Department of Ophthalmology, University of California, Davis, Sacramento 95616.
Morse
L S
LS
Toth
C A
CA
Landers
M B
MB
Hjelmeland
L M
LM
D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D014677:Pharmaceutical Vehicles / Q000633:toxicity; D010786:Photoreceptor Cells / Q000187:drug effects; D010857:Pigment Epithelium of Eye / Q000187:drug effects; D011994:Recombinant Proteins / Q000633:toxicity; D012160:Retina / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000139:chemically induced; D010959:Tissue Plasminogen Activator / Q000633:toxicity*
D014677:Pharmaceutical Vehicles; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator