دورية أكاديمية
Characterization, Stability, and in Vivo Efficacy Studies of Recombinant Human CNTF and Its Permeation Into the Neural Retina in Ex Vivo Organotypic Retinal Explant Culture Models
| العنوان: | Characterization, Stability, and in Vivo Efficacy Studies of Recombinant Human CNTF and Its Permeation Into the Neural Retina in Ex Vivo Organotypic Retinal Explant Culture Models |
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| المؤلفون: | Itkonen, Jaakko, Annala, Ada, Tavakoli, Shirin, Arango-Gonzalez, Blanca, Ueffing, Marius, Toropainen, Elisa, Ruponen, Marika, Casteleijn, Marco G, Urtti, Arto |
| المساهمون: | School of Pharmacy, Activities |
| بيانات النشر: | MDPI AG Sveitsi |
| سنة النشر: | 2020 |
| المجموعة: | University of Eastern Finland: UEF Electronic Publications |
| مصطلحات موضوعية: | retinal penetration, neuroprotection, protein aggregation, stability, intravitreal delivery, CNTF |
| الوصف: | Ciliary neurotrophic factor (CNTF) is one of the most studied neuroprotective agents withacknowledged potential in treating diseases of the posterior eye segment. Although its efficacy andmechanisms of action in the retina have been studied extensively, it is still not comprehensivelyunderstood which retinal cells mediate the therapeutic effects of CNTF. As with therapeutic proteinsin general, it is poorly elucidated whether exogenous CNTF administered into the vitreous can enterand distribute into the retina and hence reach potentially responsive target cells. Here, we havecharacterized our purified recombinant human CNTF (rhCNTF), studied the protein’sin vitrobioactivity in a cell-based assay, and evaluated the thermodynamic and oligomeric status of theprotein during storage. Biological activity of rhCNTF was further evaluatedin vivoin an animalmodel of retinal degeneration. The retinal penetration and distribution of rhCNTF after 24 h wasstudied utilizing two ex vivo retina models. Based on our characterization findings, our rhCNTFis correctly folded and biologically active. Moreover, based on initial screening and subsequentfollow-up, we identified two buffers in which rhCNTF retains its stability during storage. WhereasrhCNTF did not show photoreceptor preservative effect or improve the function of photoreceptorsin vivo, this could possibly be due to the used disease model or the short duration of action with asingle intravitreal injection of rhCNTF. On the other hand, the lack ofin vivoefficacy was shown tonot be due to distribution limitations; permeation into the retina was observed in both retinal explantmodels as in 24 h rhCNTF penetrated the inner limiting membrane, and being mostly observedin the ganglion cell layer, distributed to different layers of the neural retina. As rhCNTF can reachdeeper retinal layers, in general, having direct effects on resident CNTF-responsive target cellsis plausible. ; published version ; peerReviewed |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | Pharmaceutics; http://dx.doi.org/10.3390/pharmaceutics12070611Test; E611; 12; https://erepo.uef.fi/handle/123456789/23919Test |
| الإتاحة: | https://doi.org/10.3390/pharmaceutics12070611Test https://erepo.uef.fi/handle/123456789/23919Test |
| حقوق: | CC BY 4.0 ; openAccess ; © 2020 by the authors ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.BA893061 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |