Long-term oral administration of naringenin counteracts aging-related retinal degeneration via regulation of mitochondrial dynamics and autophagy

Abstract

Aging-related retinal degeneration can manifest as decreased visual function due to damage to retinal structures and dysfunction in retinal homeostasis. Naringenin, a flavonoid, has beneficial effects in preventing cellular aging, preserving the functionality of photoreceptors, and slowing down visual function loss. However, the role and potential mechanism of naringenin in the aging mouse retina require further investigation. In this study, we evaluated the effects of naringenin on the aging eye using electroretinogram (ERG) and hematoxylin and eosin staining and explored its potential mechanism by western blotting. ERG showed that naringenin increased the amplitude of the a- and b-waves of scotopic 3.0, 10.0, and the a-wave amplitude of photopic 3.0 in the aging mouse retina. Furthermore, administration of naringenin prevented aging-induced retinal degeneration in the total retina, ganglion cell, inner plexiform layer, inner nuclear layer, and outer nuclear layer. The expression of mitochondrial fusion protein two was increased, OPA1 protein expression and the ratio of L-OPA1/S-OPA1 were unchanged, and dynamin-related protein one was decreased in the 12-month-old mice treated with naringenin compared with the 12-month-old mice treated with vehicle. Furthermore, the downregulation of age-related alterations in autophagy was significantly rescued in the aging mice by treatment with naringenin. Taken together, these results suggest that the oral administration of naringenin improves visual function, retinal structure, mitochondrial dynamics, and autophagy in the aging mouse retinas. Naringenin may be a potential dietary supplement for the prevention or treatment of aging-related retinal degeneration.

Mitochondrial dysfunction in glaucomatous degeneration

“…It can also activate the AMPK/SIRT1/ PGC-1α pathway and decrease mTOR signaling, promoting mtDNA quality via decreased mitochondrial fragmentation and increased mitophagy [13] . Similarly, previous studies by our group elaborate that oral administration of naringenin can increase the mitochondrial fusion protein 2 and rescue the age-related downregulation of autophagy, improving the visual function and retinal structure [38] . Hence, antioxidants have displayed a strong potential to delay the progression of glaucomatous degeneration in experimental glaucoma models.…”

“…Resveratrol [13,102,112] Anti-apoptosis; Increase the expression of Opa1; Decreased mitochondrial division; Increased mitophagy; Reduce IOP Naringenin [38] Improve retinal structure and visual function…”

“…In addition, the morphology and connectivity of the mitochondrial network are controlled by the processes of mitochondrial fusion and fission, depending on the demand for specific biological needs [36][37] . Fusing together several mitochondria to produce a single mitochondrion is an example of fusion while fission refers to the process of breaking apart a single large mitochondrion into many smaller ones [38] .…”

Autophagy in the retinal neurovascular unit: New perspectives into diabetic retinopathy

“…Recent research demonstrates that naringenin treatment not only increases cone survival but also protects the retina by enhancing b‐wave amplitude 32 . This protective mechanism, according to Chen et al, may be associated with naringenin's ability to promote autophagy initiation via mTOR signaling pathway and improve mitochondrial dynamics mediate 33 . Furthermore, Sirtuin1, a gene involved in retinal degeneration, has been shown to mediate cardiomyocyte autophagy during glucose deprivation 34 .…”

“… 32 This protective mechanism, according to Chen et al, may be associated with naringenin's ability to promote autophagy initiation via mTOR signaling pathway and improve mitochondrial dynamics mediate. 33 Furthermore, Sirtuin1, a gene involved in retinal degeneration, has been shown to mediate cardiomyocyte autophagy during glucose deprivation. 34 There was a concurrent increase in sirtuin1 expression and b‐wave amplitude after 19 months of treatment for aged rats with resveratrol, an antioxidant and sirtuin1 activator, demonstrating attenuated retinal degeneration.…”