N,N-dimethyladriamycin for treatment of experimental proliferative vitreoretinopathy: efficacy and toxicity on the rabbit retina.
N,N-Dimethyladriamycin (Me-2-ADM) derives from adriamycin (doxorubicin) by N-methylation of its aminosugar moiety. In contrast to the parent agent, Me-2-ADM lacks mutagenicity and carcinogenicity. To evaluate its suitability for treatment of proliferative vitreoretinopathy (PVR), we studied the ability of Me-2-ADM to prevent traction retinal detachment in a model of PVR in rabbits. The model was created by intravitreal injection of 25,000 homologous dermal fibroblasts after vitreous gas compression. Two days after fibroblast injection, 5, 10 or 30 nmol Me-2-ADM was administered into the vitreous cavity. The control group received sham injections. All control eyes developed traction retinal detachments. Administration of 5 nmol Me-2-ADM slightly reduced the rate of retinal detachments to 90%. No retinal detachments occurred in the group treated with 10 nmol Me-2-ADM while 11% of eyes treated with 30 nmol Me-2-ADM developed retinal detachments. At day 28 of the study, light microscopic examination of retinas treated with 30 nmol Me-2-ADM revealed severe retinal damage while no such damage was present in eyes treated with 10 nmol. To exclude early retinal damage, 10 nmol Me-2-ADM were injected into eyes that had undergone vitreous gas compression but no fibroblast injection. On day 3, 7, and 14 after drug administration, ERGs were recorded simultaneously from drug treated and sham treated (contralateral) eyes. Light microscopy and transmission electron microscopy (TEM) were performed. Only transient ERG changes were observed at day 7, which recovered by day 14. All morphological findings in drug exposed eyes were in the range of normal when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710.
U H
UH
Steinhorst
E P
EP
Chen
R
R
Machemer
D L
DL
Hatchell
D000818:Animals; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D004596:Electroretinography / Q000187:drug effects; D005128:Eye Diseases / Q000188:drug therapy*; D005260:Female; D008297:Male; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000648:ultrastructure; D012163:Retinal Detachment / Q000517:prevention & control; D012164:Retinal Diseases / Q000188:drug therapy* / Q000473:pathology; D014822:Vitreous Body / Q000473:pathology
C024887:N,N-dimethyldoxorubicin; D004317:Doxorubicin