Assessment of Ocriplasmin Effects on the Vitreoretinal Compartment in Porcine and Human Model Systems

Abstract

Ocriplasmin (Jetrea®) is a recombinant protease used to treat vitreomacular traction. To gain insight into vitreoretinal observations reported after ocriplasmin treatment, we have developed an in vivo porcine ocriplasmin-induced posterior vitreous detachment (PVD) model in which we investigated vitreoretinal tissues by optical coherence tomography, histology, and cytokine profiling. Eight weeks postinjection, ocriplasmin yielded PVD in 82% of eyes. Subretinal fluid (85%) and vitreous hyperreflective spots (45%) were resolved by week 3. Histological analysis of extracellular matrix (ECM) proteins such as laminin, fibronectin, and collagen IV indicated no retinal ocriplasmin-induced ECM distribution changes. Retinal morphology was unaffected in all eyes. Cytokine profiles of ocriplasmin-treated eyes were not different from vehicle. In cell-based electrical resistance assays, blood-retinal barrier permeability was altered by ocriplasmin concentrations of 6 μg/mL and higher, with all effects being nontoxic, cell-type specific, and reversible. Ocriplasmin was actively taken up by RPE and Müller cells, and our data suggest both lysosomal and transcellular clearance routes for ocriplasmin. In conclusion, transient hyperreflective spots and fluid in a porcine ocriplasmin-induced PVD model did not correlate with retinal ECM rearrangement nor inflammation. Reversible in vitro effects on blood-retinal barrier permeability provide grounds for a hypothesis on the mechanisms behind transient subretinal fluid observed in ocriplasmin-treated patients.

Xentry-Gap19 inhibits Connexin43 hemichannel opening especially during hypoxic injury

“…In nAMD, choroidal endothelial cell damage results in vascular permeability and loss of BRB integrity due to RPE cell death [37,38]. Primary hRMEC and immortalized ARPE-19 cultures present similar physiological characteristics to the inner and outer BRB, respectively [39][40][41], while also expressing functional Cx43 HC. They are thus ideal to assess the efficacy of Cx43 HC blockers [25,42] as a potential treatment for nAMD or similar indications.…”

Mikrostrukturelle retinale Veränderungen nach pharmakologischer Vitreolyse mit Ocriplasmin – eine SD-OCT-gestützte Analyse

“…PVD ist ein natürlicher Prozess, der als harmlos einzustufen ist. (Mec-Slomska et al, 2017 In ( Khan and Haller, 2016, Itoh et al, 2014, Jonckx et al, 2017, Zhang et al, 2018, Singh et al, 2014, Madi et al, 2016 In Abb. 11: Veränderungen membrana limitans externa (ELM) und der Ellipsoidzone (EZ) prä-und postoperativ.…”