ArticleScientific reports2016
Olaparib significantly delays photoreceptor loss in a model for hereditary retinal degeneration.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- Differential effects of HDAC inhibitors in the RhoCell death discovery · 2025Article
- PARP Activity Is Essential for Retinal Photoreceptor Survival in the Human Homologous RhoJournal of neurochemistry · 2025Article
- Protein kinase G inhibition preserves photoreceptor viability and function in a new mouse model for autosomal dominant retinitis pigmentosa.Cell death & disease · 2025Article
- Deferiprone protects against photoreceptor degeneration by inhibiting parthanatos.Cell death & disease · 2025Article
- PARP inhibition preserves cone photoreceptors in rd2 retina.Acta neuropathologica communications · 2025Article
- Piceid Octanoate Protects Retinal Cells against Oxidative Damage by Regulating the Sirtuin 1/Poly-ADP-Ribose Polymerase 1 Axis In Vitro and in rd10 Mice.Antioxidants (Basel, Switzerland) · 2024Article
- Determining Photoreceptor Cell Identity: Rod Versus Cone Fate Governed by tbx2b Opposing nrl.Investigative ophthalmology & visual science · 2024Article
- Inherited Retinal Degeneration: Towards the Development of a Combination Therapy Targeting Histone Deacetylase, Poly (ADP-Ribose) Polymerase, and Calpain.Biomolecules · 2023Article
- HDAC inhibition delays photoreceptor loss inPeerJ · 2023Article
- The role of epigenetic changes in the pathology and treatment of inherited retinal diseases.Frontiers in cell and developmental biology · 2023Review
- Role of Nuclear NADAdvances in experimental medicine and biology · 2023Review
- Dynamic lipid turnover in photoreceptors and retinal pigment epithelium throughout life.Progress in retinal and eye research · 2022Review
- Reduced nuclear NAD+ drives DNA damage and subsequent immune activation in the retina.Human molecular genetics · 2022Article
- Visualizing Cell Death in Live Retina: Using Calpain Activity Detection as a Biomarker for Retinal Degeneration.International journal of molecular sciences · 2022Article
- Inherited Retinal Degeneration: PARP-Dependent Activation of Calpain Requires CNG Channel Activity.Biomolecules · 2022Article
- Olaparib, a PARP-1 inhibitor, protects retinal cells from ocular hypertension-associated oxidative damage.Frontiers in cell and developmental biology · 2022Article
- Review
- Article
- Programmed Non-Apoptotic Cell Death in Hereditary Retinal Degeneration: Crosstalk between cGMP-Dependent Pathways and PARthanatos?International journal of molecular sciences · 2021Review
- Enhancer of Zeste Homolog 2 (EZH2) Contributes to Rod Photoreceptor Death Process in Several Forms of Retinal Degeneration and Its Activity Can Serve as a Biomarker for Therapy Efficacy.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The enzyme poly-ADP-ribose-polymerase (PARP) mediates DNA-repair and rearrangements of the nuclear chromatin. Generally, PARP activity is thought to promote cell survival and in recent years a number of PARP inhibitors have been clinically developed for cancer treatment. Paradoxically, PARP activity is also connected to many diseases including the untreatable blinding disease Retinitis Pigmentosa (RP), where PARP activity appears to drive the pathogenesis of photoreceptor loss. We tested the efficacy of three different PARP inhibitors to prevent photoreceptor loss in the rd1 mouse model for RP. In retinal explant cultures in vitro, olaparib had strong and long-lasting photoreceptor neuroprotective capacities. We demonstrated target engagement by showing that olaparib reduced photoreceptor accumulation of poly-ADP-ribosylated proteins. Remarkably, olaparib also reduced accumulation of cyclic-guanosine-monophosphate (cGMP), a characteristic marker for photoreceptor degeneration. Moreover, intravitreal injection of olaparib in rd1 animals diminished PARP activity and increased photoreceptor survival, confirming in vivo neuroprotection. This study affirms the role of PARP in inherited retinal degeneration and for the first time shows that a clinically approved PARP inhibitor can prevent photoreceptor degeneration in an RP model. The wealth of human clinical data available for olaparib highlights its strong potential for a rapid clinical translation into a novel RP treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.