A Nutraceutical Strategy to Slowing Down the Progression of Cone Death in an Animal Model of Retinitis Pigmentosa

Abstract

Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by progressive degeneration of the visual cells and abnormalities in retinal pigment epithelium, the vision is lost slowly, and the final outcome is total blindness. RP primarily affects rods, but cones can also be affected as a secondary effect. Photoreceptor cell death is usually triggered by apoptosis, however the molecular mechanisms linking the rod degeneration to the secondary cone death are poorly understood. Possible causes of the secondary cone death are oxidative stress and/ or the release of toxic factors from dying rods. The aim of this study is to analyze the effect of nutraceutical molecules with antioxidant properties, on the progression of the disease in an established animal model of RP, and rd10 mice. We show that chronic treatment per os with a flavanone (naringenin) or a flavonol (quercetin) present in citrus fruits, grapes and apples, preserves retinal morphology, and ameliorates functionality. These actions are associated with a significant reduction of stress-oxidative markers, such as the detoxifying enzymes Sod1 and Sod2. In addition, naringenin and quercetin treatment reduces the levels of acrolein staining associated with a reduction of ROS in the cellular environment. The study demonstrates the beneficial effects of naringenin and quercetin, two molecules that possess antioxidant properties, limiting neurodegeneration, and thus preventing cone damage.

Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and its Inhibition by Antioxidants

“…Furthermore, interaction between photoreceptors and RPE cells is critical for maintaining visual function, and its alteration can lead to compromised vision. Our group has already demonstrated that antioxidants can delay photoreceptor degeneration in a mouse model of retinitis pigmentosa [21][22][23], and this protective effect certainly requires the integrity of RPE [24,25].…”

The Citrus Flavonoid Naringenin Protects the Myocardium from Ageing-Dependent Dysfunction: Potential Role of SIRT1

“…The diluted solutions were daily prepared; moreover, mice were weekly weighted, and water intake was daily monitored during the six-month treatment. The dosage of NAR (100 mg/kg) has been selected based on previous in vivo experiments [13,27] and in accordance with papers of others [28][29][30][31]. In particular, NAR has been dissolved in DMSO 40 mg/mL and diluted in water up to 0.4 mg/mL, to assure a daily dosage of 100 mg/kg.…”

Oxidative Stress, a Crossroad Between Rare Diseases and Neurodegeneration

“…Some of these approaches try to correct or replace the genetic defect (gene or stem cell-based therapies) or to slow down the IRD progression (nutritional supplements, neurotrophic factors, antioxidants, etc.). In particular, several antioxidant formulations including curcumin, Tauroursodeoxycholic Acid (TUDCA), vitamin A, vitamin A in combination with docosahexaenoic acid (DHA), lutein, etc., have been used to mitigate the degenerative process in RP models and patients [116,[144][145][146][147][148][149][150].…”

“…Antioxidants 2020, 9, x FOR PEER REVIEW 6 of 28 with docosahexaenoic acid (DHA), lutein, etc., have been used to mitigate the degenerative process in RP models and patients [116,[144][145][146][147][148][149][150]. 4.…”