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Declan Ciaran Murphy, Majed Felembam, Nicola Hunt, Stuart N Baker, Majlinda Lako, David Steel; Does intravitreal Ocriplasmin degrade intraretinal extracellular matrix molecules?. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3693.
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© ARVO (1962-2015); The Authors (2016-present)
Ocriplasmin (OCP), a recombinant truncated form of plasmin, is a non-specific protease which results in vitreoretinal (VR) separation in a proportion of patients with vitreomacular traction thought to be by its action on extracellular matrix (ECM) molecules at the VR interface. Outer-retinal complications such as photoreceptor dysfunction have been reported after OCP and hypothesized to result from off target effects. We carried out an experimental study to investigate the effect of OCP on a variety of retinal ECM molecules in primate eyes.
Six eyes of rhesus macaque primates were enucleated immediately post mortem after intracardiac perfusion with phosphate buffered saline. Two eyes were injected with 62.5 mcg of OCP with a 30g needle in the mid vitreous cavity, then immediately placed in carboxy perfused aCSF for 24hrs at room temperature before fixation in 4% paraformaldehyde (PFA) with removal of the anterior segment (OCP treated group). Four control eyes were used: Two eyes were placed into carboxy perfused artificial cerebrospinal fluid (aCSF) for 24 hours before PFA fixation (Control aCSF). Two further eyes underwent PFA perfusion and were immediately placed in PFA after enucleation (Control fixed). All eyes were wax embedded and horizontally sectioned at 7-8um through the macula. Immunohistochemistry with quantification using Image J software was performed to detect and quantify the following: Panlaminin, Laminin5, Laminin chains α4 and γ3, Fibronectin and Collagen IV.Antibody levels were compared across the 10 retinal layers from Bruchs membrane to the ILM using two way ANOVA with the two control groups compared to the OCP treated group
The control aCSF globes had well preserved retinal anatomy compared to the control fixed globes with an attached vitreous. There was vitreomacular separation over the macula in the OCP treated eyes suggesting that a therapeutic dose had been given. Fibronectin and panlaminin had highest expression in the ILM in the OCP treated group (P=0.0055 and 0.0150 respectively) (Figure 1 showing panlaminin results).There were no other significant differences in expression levels.
There was no evidence for any outer retinal effect of OCP or higher specificity to any of the laminin subtypes with the dose of OCP administered. The high levels of laminin and fibronectin in the ILM despite vitreoretinal separation in the OCP group was unexpected.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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