The role of recombinant lysine-plasminogen and recombinant urokinase and sulfur hexafluoride combination in inducing posterior vitreous detachment.
OBJECTIVE
To determine the optimal method of generating plasmin in vitreous using recombinant lysine-plasminogen and recombinant urokinase and to determine its efficacy in inducing posterior vitreous detachment when combined with sulfur hexafluoride.


METHODS
Plasmin concentration of the rabbit vitreous after separate and combined intravitreal administrations of recombinant lysine-plasminogen and recombinant urokinase was tested in 78 rabbits to determine the optimal method of administration. The safety and efficacy of these agents and sulfur hexafluoride in inducing complete posterior vitreous detachment (total separation of the vitreous apart from vitreous base) were also evaluated.


RESULTS
The highest plasmin concentration in vitreous was measured 10 minutes after injection. Intravitreal administration of recombinant lysine-plasminogen and recombinant urokinase did not cause any toxicity findings up to concentrations of 100 microg and 200 IU, respectively, on funduscopy, electroretinography, and histopathologic studies. When combined with sulfur hexafluoride injection, separate intravitreal administrations of 75 microg/0.1 mL of recombinant lysine-plasminogen and 15 IU/0.1 mL of recombinant urokinase induced complete posterior vitreous detachment in 75% of the eyes compared with 13% in eyes that received sulfur hexafluoride injection combined with balanced salt solution, recombinant lysine-plasminogen, or recombinant urokinase.


CONCLUSIONS
Plasmin was effectively generated in the vitreous after separate intravitreal administrations of recombinant lysine-plasminogen and recombinant urokinase. When combined with intravitreal gas injection, this method of plasmin production induced complete posterior vitreous detachment in 75% of the eyes.
Men
Gamze
G
Department of Ophthalmology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
Peyman
Gholam A
GA
Genaidy
Mahmoud
M
Kuo
Po-Cheng
PC
Ghahramani
Fatemah
F
Blake
Diane A
DA
Bezerra
Yanno
Y
Naaman
Georges
G
Figueiredo
Eduardo
E
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005341:Fibrinolysin / Q000096:biosynthesis*; D008855:Microscopy, Electron, Scanning; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D010958:Plasminogen / Q000008:administration & dosage* / Q000009:adverse effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage; D012160:Retina / Q000648:ultrastructure; D013459:Sulfur Hexafluoride / Q000008:administration & dosage*; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D014822:Vitreous Body / Q000378:metabolism* / Q000648:ultrastructure; D020255:Vitreous Detachment / Q000139:chemically induced*
D004338:Drug Combinations; D010446:Peptide Fragments; D011994:Recombinant Proteins; C018998:lysyl-plasminogen; D010958:Plasminogen; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D013459:Sulfur Hexafluoride