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Pyrroloquinoline Quinone Protects Against Light-Induced Retinal Damage in Association with the Suppression of c-Fos
Hinata Ozawa1, Eriko Sugano1,2, Kitako Tabata1
1Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Division of Science and Engineering, Iwate University, 4-3-5 Ueda, Morioka 020-8551, Japan.
Abstract:
Age-related macular degeneration (AMD) is a progressive retinal disorder characterised by oxidative stress and inflammation. Although pyrroloquinoline quinone (PQQ) has been reported to exert neuroprotective effects, its specific efficacy in in vivo models of AMD pathophysiology has not yet been elucidated. In this study, we evaluated the protective effects of PQQ against all-trans-retinal (ATR)-induced cytotoxicity in ARPE-19 cells and light-induced photoreceptor degeneration in rats. Pretreatment of ARPE-19 cells with PQQ dose-dependently mitigated ATR-induced cytotoxicity. In the in vivo model, rats received a single intraperitoneal injection of PQQ (2 or 5 mg/kg) 1 h prior to 1000-lux light exposure. Retinal function and morphology were evaluated by electroretinography and haematoxylin-eosin staining, respectively. The 5 mg/kg PQQ group retained significantly greater retinal function than the vehicle group at 3 days postexposure and demonstrated significant preservation of the outer nuclear layer at 7 days postexposure, indicating the suppression of photoreceptor cell death. Western blot analysis detected the dose-dependent suppression of light-induced c-Fos upregulation following PQQ treatment. These findings suggest that the protective effect of PQQ against phototoxic damage is associated with the suppression of c-Fos signalling, thus lending support to the further investigation of PQQ as a potential therapeutic agent for AMD.
Insights
Pyrroloquinoline quinone (PQQ) protects against retinal damage in cell and rat models of age-related macular degeneration (AMD). PQQ treatment suppressed photoreceptor cell death and preserved retinal function, suggesting therapeutic potential for AMD.
Area of Science:
- Ophthalmology
- Neuroscience
- Pharmacology
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by oxidative stress and inflammation.
- Pyrroloquinoline quinone (PQQ) is known for its neuroprotective properties, but its efficacy in AMD models is not well-established.
Purpose of the Study:
- To investigate the protective effects of PQQ against retinal damage in cellular and animal models relevant to AMD.
- To explore the underlying mechanisms of PQQ's action in mitigating phototoxic injury.
Main Methods:
- ARPE-19 cells were treated with PQQ and exposed to all-trans-retinal (ATR) to assess cytotoxicity.
- Rats were treated with PQQ and exposed to high-intensity light to induce photoreceptor degeneration.
- Retinal function was evaluated using electroretinography, and retinal morphology was assessed via haematoxylin-eosin staining.
- Western blot analysis was used to examine the expression of c-Fos.
Main Results:
- PQQ dose-dependently reduced ATR-induced cytotoxicity in ARPE-19 cells.
- PQQ treatment in rats significantly preserved retinal function and outer nuclear layer morphology after light exposure.
- PQQ administration suppressed the upregulation of c-Fos, a marker of cellular stress, in a dose-dependent manner.
Conclusions:
- PQQ exhibits significant protective effects against phototoxic damage in both cellular and in vivo models of AMD.
- The findings suggest that PQQ's therapeutic benefits in AMD may be mediated through the suppression of c-Fos signaling.
- PQQ warrants further investigation as a potential therapeutic agent for age-related macular degeneration.
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