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Toward smart design of retinal drug carriers : a novel bovine retinal explant model to study the barrier role of the vitreoretinal interface

(2017) DRUG DELIVERY. 24(1). p.1384-1394
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Abstract
Retinal gene delivery via intravitreal injection is hampered by various physiological barriers present in the eye of which the vitreoretinal (VR) interface represents the most serious hurdle. In this study, we present a retinal explant model especially designed to study the role of this interface as a barrier for the penetration of vectors into the retina. In contrast to all existing explant models, the developed model is bovine-derived and more importantly, keeps the vitreous attached to the retina at all times to guarantee an intact VR interface. After ex vivo intravitreal injection into the living retinal explant, the route of fluorescent carriers across the VR interface can be tracked. By applying two different imaging methods on this model, we discovered that the transfer through the VR barrier is size-dependent since 40 nm polystyrene particles are more easily taken up in the retina than 100 and 200 nm sized particles. In addition, we found that removing the vitreous, as commonly done for culture of conventional explants, leads to an overestimation of particle uptake, and conclude that the ultimate barrier to overcome for retinal uptake is undoubtedly the inner limiting membrane. Damaging this matrix resulted in a massive increase in particle transfer into the retina. In conclusion, we have developed a highly relevant ex vivo model that maximally mimics the human in vivo physiology which can be applied as a representative test set-up to assess the potential of promising drug delivery carriers to cross the VR interface.
Keywords
Vitreoretinal interface, retinal gene delivery, inner limiting membrane, vitreous, retinal explant, ex vivo, large animal, nanoparticle, GENE DELIVERY, INTRAVITREAL INJECTION, PIGMENT EPITHELIUM, LIMITING MEMBRANE, BASEMENT-MEMBRANE, HYALURONIC-ACID, VITREOUS-HUMOR, AAV VECTORS, THERAPY, NANOPARTICLES

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Citation

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MLA
Peynshaert, Karen, et al. “Toward Smart Design of Retinal Drug Carriers : A Novel Bovine Retinal Explant Model to Study the Barrier Role of the Vitreoretinal Interface.” DRUG DELIVERY, vol. 24, no. 1, 2017, pp. 1384–94, doi:10.1080/10717544.2017.1375578.
APA
Peynshaert, K., Devoldere, J., Forster, V., Picaud, S., Vanhove, C., De Smedt, S., & Remaut, K. (2017). Toward smart design of retinal drug carriers : a novel bovine retinal explant model to study the barrier role of the vitreoretinal interface. DRUG DELIVERY, 24(1), 1384–1394. https://doi.org/10.1080/10717544.2017.1375578
Chicago author-date
Peynshaert, Karen, Joke Devoldere, Valérie Forster, Serge Picaud, Christian Vanhove, Stefaan De Smedt, and Katrien Remaut. 2017. “Toward Smart Design of Retinal Drug Carriers : A Novel Bovine Retinal Explant Model to Study the Barrier Role of the Vitreoretinal Interface.” DRUG DELIVERY 24 (1): 1384–94. https://doi.org/10.1080/10717544.2017.1375578.
Chicago author-date (all authors)
Peynshaert, Karen, Joke Devoldere, Valérie Forster, Serge Picaud, Christian Vanhove, Stefaan De Smedt, and Katrien Remaut. 2017. “Toward Smart Design of Retinal Drug Carriers : A Novel Bovine Retinal Explant Model to Study the Barrier Role of the Vitreoretinal Interface.” DRUG DELIVERY 24 (1): 1384–1394. doi:10.1080/10717544.2017.1375578.
Vancouver
1.
Peynshaert K, Devoldere J, Forster V, Picaud S, Vanhove C, De Smedt S, et al. Toward smart design of retinal drug carriers : a novel bovine retinal explant model to study the barrier role of the vitreoretinal interface. DRUG DELIVERY. 2017;24(1):1384–94.
IEEE
[1]
K. Peynshaert et al., “Toward smart design of retinal drug carriers : a novel bovine retinal explant model to study the barrier role of the vitreoretinal interface,” DRUG DELIVERY, vol. 24, no. 1, pp. 1384–1394, 2017.
@article{8531752,
  abstract     = {{Retinal gene delivery via intravitreal injection is hampered by various physiological barriers present in the eye of which the vitreoretinal (VR) interface represents the most serious hurdle. In this study, we present a retinal explant model especially designed to study the role of this interface as a barrier for the penetration of vectors into the retina. In contrast to all existing explant models, the developed model is bovine-derived and more importantly, keeps the vitreous attached to the retina at all times to guarantee an intact VR interface. After ex vivo intravitreal injection into the living retinal explant, the route of fluorescent carriers across the VR interface can be tracked. By applying two different imaging methods on this model, we discovered that the transfer through the VR barrier is size-dependent since 40 nm polystyrene particles are more easily taken up in the retina than 100 and 200 nm sized particles. In addition, we found that removing the vitreous, as commonly done for culture of conventional explants, leads to an overestimation of particle uptake, and conclude that the ultimate barrier to overcome for retinal uptake is undoubtedly the inner limiting membrane. Damaging this matrix resulted in a massive increase in particle transfer into the retina. In conclusion, we have developed a highly relevant ex vivo model that maximally mimics the human in vivo physiology which can be applied as a representative test set-up to assess the potential of promising drug delivery carriers to cross the VR interface.}},
  author       = {{Peynshaert, Karen and Devoldere, Joke and Forster, Valérie and Picaud, Serge and Vanhove, Christian and De Smedt, Stefaan and Remaut, Katrien}},
  issn         = {{1071-7544}},
  journal      = {{DRUG DELIVERY}},
  keywords     = {{Vitreoretinal interface,retinal gene delivery,inner limiting membrane,vitreous,retinal explant,ex vivo,large animal,nanoparticle,GENE DELIVERY,INTRAVITREAL INJECTION,PIGMENT EPITHELIUM,LIMITING MEMBRANE,BASEMENT-MEMBRANE,HYALURONIC-ACID,VITREOUS-HUMOR,AAV VECTORS,THERAPY,NANOPARTICLES}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{1384--1394}},
  title        = {{Toward smart design of retinal drug carriers : a novel bovine retinal explant model to study the barrier role of the vitreoretinal interface}},
  url          = {{http://doi.org/10.1080/10717544.2017.1375578}},
  volume       = {{24}},
  year         = {{2017}},
}

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