Zusammenfassung
Hintergrund
Microplasmin (Thrombo-Genics Ltd., Dublin, Irland) ist ein rekombinanter Wirkstoff, bestehend aus der katalytischen Domäne von humanem Plasmin. Wir untersuchten post mortem et in vivo, ob Microplasmin eine hintere Glaskörperabhebung induzieren kann, und ob mit morphologischen oder funktionellen Netzhautveränderungen zu rechnen ist.
Methode
In humanen Spenderaugen und in vivo bei Kaninchen, Minipig, Katze und Primaten wurde Microplasmin intravitreal appliziert und der Grad der vitreoretinalen Separation standardisiert mittels Rasterelektronenmikroskopie bestimmt. Zusätzlich wurden die Techniken der Transmissionselektronenmikroskopie, der konfokalen Mikroskopie und der Elektroretinographie (ERG) angewandt.
Resultate
Microplasmin kann post mortem et in vivo eine vollständige und dosisabhängige hintere Glaskörperabhebung induzieren. Morphologische oder immunzytochemische Netzhautveränderungen finden sich nicht. Dauerhafte ERG-Veränderungen sind nicht nachzuweisen.
Schlussfolgerung
Microplasmin trennt den Glaskörper von der Netzhaut ohne morphologische oder funktionelle Netzhautveränderungen zu induzieren. Mit diesen präklinischen Ergebnissen führen wir derzeit die ersten klinischen Studien zur Microplasmin-assistierten Vitrektomie durch.
Summary
Background
Microplasmin (ThromboGenics Ltd., Dublin, Ireland) is a recombinant molecule consisting of the catalytic domain of human plasmin. We investigated the cleaving effect of microplasmin at the vitreoretinal interface in post mortem eyes and in vivo.
Methods
Microplasmin was injected into the vitreous of post mortem eyes and in different animal models. The vitreoretinal interface was investigated by scanning and transmission electron microscopy and by laser scanning microscopy. In vivo, electroretinography was also performed.
Results
Microplasmin separates the vitreous from the retina in a dose-dependent fashion. The retinal architecture including the ultrastructure of the inner and outer retina is well preserved. There are no alterations of retinal morphology and immunocytochemistry between treated eyes and control eyes.
Conclusion
Microplasmin cleaves the vitreoretinal junction and helps to completely separate the vitreous from the retina. Several clinical trials are currently underway.
Similar content being viewed by others
Literatur
Bhisitkul RB (2001) Anticipation for enzymatic vitreolysis. Br J Ophthalmol 85: 1–2
Sebag J (1998) Pharmacologic vitreolysis. Retina 18: 1–3
Nasrallah FP, Jalkh AE, Van Coppenolle F, Kado M, Trempe CL, McMeel JW, Schepens CL (1988) The role of the vitreous in diabetic macular edema. Ophthalmology 95: 1335–1339
Hikichi T, Fujio N, Akiba J, Azuma Y, Takahashi M, Yoshida A (1997) Association between the short-term natural history of diabetic macular edema and the vitreomacular relationship in type II diabetes mellitus. Ophthalmology 104: 473–478
Capeans C, Lorenzo J, Santos L, Suarez A, Copena MJ, Blanco MJ, Sanchez-Salorio M (1998) Comparative study of incomplete posterior vitreous detachment as a risk factor for proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 236: 481–5
Bonnet M (1988) The development of severe proliferative vitreoretinopathy after retinal detachment surgery. Grade B: a determining risk factor. Graefes Arch Clin Exp Ophthalmol 226: 201–5
Tolentino FI, Schepens CL, Freeman HM (1967) Massive preretinal retraction. A biomicroscopic study. Arch Ophthalmol 78: 16–22
Sebag J (1996) Diabetic vitreopathy. Ophthalmology 103: 205–206
Hageman GS, Russell SR (1994) Chondroitinase-mediated disinsertion of the primate vitreous body. Invest Ophthalmol Vis Sci 35: 1260
Hikichi T, Kado M, Yoshida A (2000) Intravitreal injection of hyaluronidase cannot induce posterior vitreous detachment in the rabbit. Retina 20: 195–8
Sebag J (2002) Is pharmacologic vitreolysis brewing. Retina 22: 1–3
Stenn KS, Link R, Moelmann G (1989) Dispase, a neutral protease from Bacillus polymyxa, is a powerful fibronectinase and type IV collagenase. J Invest Dermatol 93: 287–290.
Tezel TH, Del Priore LV, Kaplan HJ (1998) Posterior vitreous detachment with dispase. Retina 18: 7–15
Oliveira LB, Tatebayashi M, Mahmoud TH, Blackmon SM, Wong F, McCuen BW (2001) 2nd. Dispase facilitates posterior vitreous detachment during vitrectomy in young pigs. Retina 21: 324–31
Jorge R, Oyamaguchi EK, Cardillo JA, Gobbi A, Laicine EM, Haddad A (2003) Intravitreal injection of dispase causes retinal hemorrhages in rabbit and human eyes. Curr Eye Res 26: 107–12
Verstraeten TC, Chapman C, Hartzer M, Winkler BS, Trese MT, Williams GA (1993) Pharmacologic induction of posterior vitreous detachment in the rabbit. Arch Ophthalmol 111: 849–854
Gandorfer A, Putz E, Welge-Lussen U, Gruterich M, Ulbig M, Kampik A (2001) Ultrastructure of the vitreoretinal interface following plasmin assisted vitrectomy. Br J Ophthalmol 85: 6–10
Gandorfer A, Priglinger S, Schebitz K, Hoops J, Ulbig M, Ruckhofer J, Grabner G, Kampik A (2002) Vitreoretinal morphology of plasmin-treated human eyes. Am J Ophthalmol 133: 156–9
Gandorfer A, Ulbig M, Kampik A (2002) Plasmin-assisted vitrectomy eliminates cortical vitreous remnants. Eye 16: 95–7
Gandorfer A, Rohleder M, Sethi C, Eckle D, Welge-Lussen U, Kampik A, Luthert P, Charteris D (2004) Posterior vitreous detachment induced by microplasmin. Invest Ophthalmol Vis Sci 45: 641–7
Gandorfer A, Rohleder M, Grosselfinger S, Haritoglou C, Ulbig M, Kampik A (2005) Epiretinal pathology of diffuse diabetic macular edema associated with vitreomacular traction. Am J Ophthalmol 139: 638–52
Gandorfer A, Rohleder M, Kampik A (2002) Epiretinal pathology of vitreomacular traction syndrome. Br J Ophthalmol 86: 902–9
Uemura A, Nakamura M, Kachi S, Nishizawa Y, Asami T, Miyake Y, Terasaki H (2005) Effect of plasmin on laminin and fibronectin during plasmin-assisted vitrectomy. Arch Ophthalmol 123: 209–13
Kohno T, Sorgente N, Ishibashi T, Goodnight R, Ryan SJ (1987) Immunofluorescent studies of fibronectin and laminin in the human eye. Invest Ophthalmol Vis Sci 28: 506–514
Yoshida A, Ishiguro S, Tamai M (1993) Expression of glial fibrillic acidic protein in rabbit müller cells after lensectomy-vitrectomy. Invest Ophthalmol Vis Sci 34: 3154–3160
Ansari RR, Suh KI, Sebag J (2002) Dynamic light scattering (DLS) quantifies the effects of microplasmin pharmacologic vitreolysis. Poster at the 5th International Symposium on Ocular Pharmacology and Therapeutics (ISOPT). Monte Carlo, 2004
Staubach F, Nober V, Janknecht P (2004) Enzyme-assisted vitrectomy in enucleated pig eyes: a comparison of hyaluronidase, chondroitinase, and plasmin. Curr Eye Res 29: 261–8
Trese M (2002) Enzymatic-assisted vitrectomy. Eye 16: 365–368
Trese MT, Williams GA, Hartzer MK (2000) A new approach to stage 3 macular holes. Ophthalmology 107: 1607–1611
Williams JG, Trese MT, Williams GA, Hartzer MK (2001) Autologous plasmin enzyme in the surgical management of diabetic retinopathy. Ophthalmology 108: 1902–1905
Margherio AR, Margherio RR, Hartzer M, Trese MT, Williams GA, Ferrone PJ (1998) Plasmin enzyme-assisted vitrectomy in traumatic pediatric macular holes. Ophthalmology 105: 1617–1620
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gandorfer, A., Kampik, A. Plasmin-assistierte Vitrektomie — Stand der Forschung und klinische Evaluation. Spektrum Augeheilkd 19, 221–224 (2005). https://doi.org/10.1007/BF03163401
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03163401