Assessment of Ocriplasmin Effects on the Vitreoretinal Compartment in Porcine and Human Model Systems
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 vitr...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Ophthalmology |
| Online Access: | http://dx.doi.org/10.1155/2017/2060765 |
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| author | Bart Jonckx Michael Porcu Aurelie Candi Isabelle Etienne Philippe Barbeaux Jean H. M. Feyen |
| author_facet | Bart Jonckx Michael Porcu Aurelie Candi Isabelle Etienne Philippe Barbeaux Jean H. M. Feyen |
| author_sort | Bart Jonckx |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d3597cb2f05943a8bfa95879a6bbae84 |
| institution | Kabale University |
| issn | 2090-004X 2090-0058 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Ophthalmology |
| spelling | doaj-art-d3597cb2f05943a8bfa95879a6bbae842025-02-03T05:44:54ZengWileyJournal of Ophthalmology2090-004X2090-00582017-01-01201710.1155/2017/20607652060765Assessment of Ocriplasmin Effects on the Vitreoretinal Compartment in Porcine and Human Model SystemsBart Jonckx0Michael Porcu1Aurelie Candi2Isabelle Etienne3Philippe Barbeaux4Jean H. M. Feyen5ThromboGenics NV, Gaston Geenslaan 1, 3001 Leuven, BelgiumThromboGenics NV, Gaston Geenslaan 1, 3001 Leuven, BelgiumThromboGenics NV, Gaston Geenslaan 1, 3001 Leuven, BelgiumThromboGenics NV, Gaston Geenslaan 1, 3001 Leuven, BelgiumThromboGenics NV, Gaston Geenslaan 1, 3001 Leuven, BelgiumThromboGenics NV, Gaston Geenslaan 1, 3001 Leuven, BelgiumOcriplasmin (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.http://dx.doi.org/10.1155/2017/2060765 |
| spellingShingle | Bart Jonckx Michael Porcu Aurelie Candi Isabelle Etienne Philippe Barbeaux Jean H. M. Feyen Assessment of Ocriplasmin Effects on the Vitreoretinal Compartment in Porcine and Human Model Systems Journal of Ophthalmology |
| title | Assessment of Ocriplasmin Effects on the Vitreoretinal Compartment in Porcine and Human Model Systems |
| title_full | Assessment of Ocriplasmin Effects on the Vitreoretinal Compartment in Porcine and Human Model Systems |
| title_fullStr | Assessment of Ocriplasmin Effects on the Vitreoretinal Compartment in Porcine and Human Model Systems |
| title_full_unstemmed | Assessment of Ocriplasmin Effects on the Vitreoretinal Compartment in Porcine and Human Model Systems |
| title_short | Assessment of Ocriplasmin Effects on the Vitreoretinal Compartment in Porcine and Human Model Systems |
| title_sort | assessment of ocriplasmin effects on the vitreoretinal compartment in porcine and human model systems |
| url | http://dx.doi.org/10.1155/2017/2060765 |
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