PARP inhibition preserves cone photoreceptors in rd2 retina
Abstract The rd2 mouse model, characterized by a mutation in the Prph2 gene, exhibits abnormal development of photoreceptor outer segments, resulting in progressive retinal degeneration. While the correlation between poly-ADP-ribose polymerase (PARP) activity and the degeneration of rod photorecepto...
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BMC
2025-04-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-025-01982-5 |
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| author | Pakize Nur Akkaya María Miranda Inmaculada Almansa Cigdem Elmas Dragana Trifunovic Zohreh Hosseinzadeh Ayse Sahaboglu |
| author_facet | Pakize Nur Akkaya María Miranda Inmaculada Almansa Cigdem Elmas Dragana Trifunovic Zohreh Hosseinzadeh Ayse Sahaboglu |
| author_sort | Pakize Nur Akkaya |
| collection | DOAJ |
| description | Abstract The rd2 mouse model, characterized by a mutation in the Prph2 gene, exhibits abnormal development of photoreceptor outer segments, resulting in progressive retinal degeneration. While the correlation between poly-ADP-ribose polymerase (PARP) activity and the degeneration of rod photoreceptors is established in the rd2 model, the specific mechanism driving cone degeneration in this model remains unclear. Furthermore, it is yet to be determined whether inhibiting PARP activity can effectively impede the degeneration of cone photoreceptors in this context. We demonstrated that PARP inhibitors Olaparib, BMN-673, and 3-aminobenzamide (3AB), effectively reduced photoreceptor cell loss in the rd2 retina. Notably, rd2 retinas exhibited decreased cone density, but treatment with PARP inhibitors significantly protected cone photoreceptors. The PARP inhibitors, particularly BMN-673, demonstrated a significant protective effect as evidenced by increased rhodopsin expression within the outer segment and a concurrent decrease in Müller cell activity indicated by GFAP expression. The treatment also resulted in significant changes for markers of oxidative stress, such as glutathione (GSH), and oxidized glutathione (GSSG). Notably, the administration of PARP inhibitors also reduced CD9 expression (extracellular vesicle marker), which were significantly increased within the outer nuclear layer (ONL) in the rd2 retinas. Among PARP inhibitors, BMN-673 demonstrated the highest efficacy in preserving photoreceptors, particularly benefiting cone cells. Graphical Abstract |
| format | Article |
| id | doaj-art-f4e9b61f1159453b84cd2a409cdc2a75 |
| institution | DOAJ |
| issn | 2051-5960 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-f4e9b61f1159453b84cd2a409cdc2a752025-08-20T03:04:54ZengBMCActa Neuropathologica Communications2051-59602025-04-0113111910.1186/s40478-025-01982-5PARP inhibition preserves cone photoreceptors in rd2 retinaPakize Nur Akkaya0María Miranda1Inmaculada Almansa2Cigdem Elmas3Dragana Trifunovic4Zohreh Hosseinzadeh5Ayse Sahaboglu6Department of Histology-Embryology, Balikesir University Faculty of MedicineDepartamento Ciencias Biomédicas, Facultad de Ciencias de La Salud, Universidad Cardenal Herrera-CEU, CEU UniversitiesDepartamento Ciencias Biomédicas, Facultad de Ciencias de La Salud, Universidad Cardenal Herrera-CEU, CEU UniversitiesDepartment of Histology-Embryology, Gazi University Faculty of MedicineCentre for Ophthalmology, Institute for Ophthalmic Research, Eberhard Karls UniversityDepartment of Ophthalmology, Radboud University Medical CenterCentre for Ophthalmology, Institute for Ophthalmic Research, Eberhard Karls UniversityAbstract The rd2 mouse model, characterized by a mutation in the Prph2 gene, exhibits abnormal development of photoreceptor outer segments, resulting in progressive retinal degeneration. While the correlation between poly-ADP-ribose polymerase (PARP) activity and the degeneration of rod photoreceptors is established in the rd2 model, the specific mechanism driving cone degeneration in this model remains unclear. Furthermore, it is yet to be determined whether inhibiting PARP activity can effectively impede the degeneration of cone photoreceptors in this context. We demonstrated that PARP inhibitors Olaparib, BMN-673, and 3-aminobenzamide (3AB), effectively reduced photoreceptor cell loss in the rd2 retina. Notably, rd2 retinas exhibited decreased cone density, but treatment with PARP inhibitors significantly protected cone photoreceptors. The PARP inhibitors, particularly BMN-673, demonstrated a significant protective effect as evidenced by increased rhodopsin expression within the outer segment and a concurrent decrease in Müller cell activity indicated by GFAP expression. The treatment also resulted in significant changes for markers of oxidative stress, such as glutathione (GSH), and oxidized glutathione (GSSG). Notably, the administration of PARP inhibitors also reduced CD9 expression (extracellular vesicle marker), which were significantly increased within the outer nuclear layer (ONL) in the rd2 retinas. Among PARP inhibitors, BMN-673 demonstrated the highest efficacy in preserving photoreceptors, particularly benefiting cone cells. Graphical Abstracthttps://doi.org/10.1186/s40478-025-01982-5rd2 retinasPhotoreceptor cell deathPARP inhibitionCone degenerationRetinal inflammation |
| spellingShingle | Pakize Nur Akkaya María Miranda Inmaculada Almansa Cigdem Elmas Dragana Trifunovic Zohreh Hosseinzadeh Ayse Sahaboglu PARP inhibition preserves cone photoreceptors in rd2 retina Acta Neuropathologica Communications rd2 retinas Photoreceptor cell death PARP inhibition Cone degeneration Retinal inflammation |
| title | PARP inhibition preserves cone photoreceptors in rd2 retina |
| title_full | PARP inhibition preserves cone photoreceptors in rd2 retina |
| title_fullStr | PARP inhibition preserves cone photoreceptors in rd2 retina |
| title_full_unstemmed | PARP inhibition preserves cone photoreceptors in rd2 retina |
| title_short | PARP inhibition preserves cone photoreceptors in rd2 retina |
| title_sort | parp inhibition preserves cone photoreceptors in rd2 retina |
| topic | rd2 retinas Photoreceptor cell death PARP inhibition Cone degeneration Retinal inflammation |
| url | https://doi.org/10.1186/s40478-025-01982-5 |
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