Academic Journal
New in vitro cellular model for molecular studies of retinitis pigmentosa
| العنوان: | New in vitro cellular model for molecular studies of retinitis pigmentosa |
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| المؤلفون: | Huang L., Kutluer M., Adani E., Comitato A., Marigo V. |
| المساهمون: | Huang, L., Kutluer, M., Adani, E., Comitato, A., Marigo, V. |
| سنة النشر: | 2021 |
| المجموعة: | Archivio della ricerca dell'Università di Modena e Reggio Emilia (Unimore: IRIS) |
| مصطلحات موضوعية: | 661W, Neuroprotection, Retinal degeneration, Rod photoreceptor, Animal, Basic-Leucine Zipper Transcription Factor, Biomarker, Cell Line, Cells, Cultured, Cloning, Molecular, Disease Susceptibility, Eye Protein, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression, Human, Mice, Retinal Rod Photoreceptor Cell, Retinitis Pigmentosa |
| الوصف: | Retinitis pigmentosa (RP) is an inherited form of retinal degeneration characterized by primary rod photoreceptor cell death followed by cone loss. Mutations in several genes linked to the disease cause increased levels of cyclic guanosine monophosphate (cGMP) and calcium ion influxes. The purpose of this project was to develop a new in vitro photoreceptor degeneration model for molecular studies of RP. 661W cells were genetically modified to stably express the neural retina leucine zipper (NRL) transcription factor. One clone (661W-A11) was selected based on the expression of Nrl target genes. 661W-A11 showed a significant increase in expression of rod-specific genes but not of cone-specific genes, compared with 661W cells. Zaprinast was used to inhibit phosphodiesterase 6 (PDE6) activity to mimic photoreceptor degeneration in vitro. The activation of cell death pathways resulting from PDE6 inhibition was confirmed by detection of decreased viability and increased intracellular cGMP and calcium, as well as activation of protein kinase G (PKG) and calpains. In this new in vitro system, we validated the effects of previously published neuroprotective drugs. The 661W-A11 cells may serve as a new model for molecular studies of RP and for high-throughput drug screening. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/34208617; info:eu-repo/semantics/altIdentifier/wos/WOS:000666531700001; volume:22; issue:12; firstpage:6440; lastpage:6440; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; info:eu-repo/grantAgreement/EC/H2020/ND; http://hdl.handle.net/11380/1251710; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85107833654 |
| DOI: | 10.3390/ijms22126440 |
| الاتاحة: | http://hdl.handle.net/11380/1251710 https://doi.org/10.3390/ijms22126440 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.B0FF8DC2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/ijms22126440 |
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