What this means
Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy (prevalence ~1:4000) and a leading Mendelian cause of working-age blindness. Despite marked genetic heterogeneity, its progression converges on a common secondary cascade of outer-retinal hyperoxia, increased reactive oxygen species (ROS), and mitochondrial dysfunction that drives cone degeneration and central vision loss.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Earlier studies
- Kind of research
- A summary of earlier studies
The science
- Original title
- The Oxidative-Mitochondrial-Inflammatory Axis in Retinitis Pigmentosa: Extracellular mtDNA as Biomarker and Therapeutic Read-Out.
- Authors
- Grimaldi R, Franco F, Vingolo EM
- Journal
- Antioxidants (Basel, Switzerland)
- Published
- Sep 26, 2026
- Study type
- Review
- PMID
- 42792149 ↗
Abstract
Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy (prevalence ~1:4000) and a leading Mendelian cause of working-age blindness. Despite marked genetic heterogeneity, its progression converges on a common secondary cascade of outer-retinal hyperoxia, increased reactive oxygen species (ROS), and mitochondrial dysfunction that drives cone degeneration and central vision loss. Because this oxidative cascade is largely genotype-independent and pharmacologically tractable, oxidative stress is a cross-cutting therapeutic target. Within it, mitochondrial DNA (mtDNA) is a key element: once released from damaged photoreceptors-free or within exosomes-it may act as a damage-associated molecular pattern (DAMP), engaging TLR9, cGAS-STING, and the NLRP3 inflammasome and sustaining chronic neuroinflammation. Extracellular mtDNA is therefore a potential integrative marker, simultaneously reflecting oxidative stress, mitochondrial dysfunction, cell death, and innate-immune activation. A central knowledge gap, however, remains: the mechanistic steps linking mtDNA to inflammation and to photoreceptor death have not been demonstrated in RP itself, and extracellular mtDNA has never been quantified in the ocular fluids of RP patients. In this review we appraise oxidative biomarkers in RP, propose extracellular mtDNA as a candidate biomarker of disease activity, and examine antioxidant and redox-modulating therapies-from N-acetylcysteine and elamipretide trials to DAMP-sensor inhibition-across experimental and clinical models. Finally, we propose extracellular mtDNA as a candidate pharmacodynamic endpoint and outline a path toward its validation.
Grimaldi R, Franco F, Vingolo EM The Oxidative-Mitochondrial-Inflammatory Axis in Retinitis Pigmentosa: Extracellular mtDNA as Biomarker and Therapeutic Read-Out. Antioxidants (Basel, Switzerland). 2026. doi:10.3390/antiox15091110. PMID: 42792149. https://pubmed.ncbi.nlm.nih.gov/42792149/
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