Herbimycin A in the treatment of experimental proliferative vitreoretinopathy: toxicity and efficacy study.
BACKGROUND
Proliferative vitreoretinopathy (PVR) is partially caused by peptide growth factors, stimulating the cell by binding to a transmembrane tyrosine kinase receptor. We studied the effects of herbimycin A (HA), a tyrosine kinase inhibitor, in PVR.


METHODS
Toxicity studies: Electroretinography and histological studies were performed after intravitreal injection of HA. Efficacy studies: Homologous rabbit dermal fibroblasts were injected intravitreally, followed by injection of HA. The presence of tractional retinal detachment (TRD) and severity of inflammation were assessed.


RESULTS
Toxicity studies: Eyes injected with HA exhibited decrease in B-wave amplitude initially, with subsequent recovery. Histologically, damage to photoreceptors was evident after injection of high but not of low doses of HA. Efficacy studies: Inflammatory response and the development of TRD were significantly reduced with all doses of HA.


CONCLUSIONS
HA (20 microM) was found to be effective and safe in preventing the development of inflammation and TRD.
Imai
K
K
The Wilmer Ophthalmological Institute, The Johns Hopkins Hospital, Baltimore, MD 21205, USA.
Loewenstein
A
A
Koroma
B
B
Grebe
R
R
de Juan
E
E
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use* / Q000633:toxicity; D016227:Benzoquinones; D001706:Biopsy; D002478:Cells, Cultured; D004596:Electroretinography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use* / Q000633:toxicity; D005347:Fibroblasts / Q000473:pathology; D007267:Injections; D047029:Lactams, Macrocyclic; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000627:therapeutic use* / Q000633:toxicity; D011817:Rabbits; D012163:Retinal Detachment / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D017828:Rifabutin / Q000031:analogs & derivatives; D018630:Vitreoretinopathy, Proliferative / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D014822:Vitreous Body
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases