Persimmon Leaves (Diospyros kaki) Extract Protects Optic Nerve Crush-Induced Retinal Degeneration

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Abstract

Retinal ganglion cell (RGC) death is part of many retinal diseases. Here, we report that the ethanol extract of Diospyros kaki (EEDK) exhibits protective properties against retinal degeneration, both in vitro and in vivo. Upon exposure to cytotoxic compounds, RGC-5 cells showed approximately 40% cell viability versus the control, while pre-treatment with EEDK markedly increased cell viability in a concentration-dependent manner. Further studies revealed that cell survival induced by EEDK was associated with decreased levels of apoptotic proteins, such as poly (ADP-ribose) polymerase, p53, and cleaved caspase-3. In addition to apoptotic pathways, we demonstrated that expression levels of antioxidant-associated proteins, such as superoxide dismutase-1, glutathione S-transferase, and glutathione peroxidase-1, were positively modulated by EEDK. In a partial optic nerve crush mouse model, EEDK had similar ameliorating effects on retinal degeneration resulting from mechanical damages. Therefore, our results suggest that EEDK may have therapeutic potential against retinal degenerative disorders, such as glaucoma.

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The role of oxidative stress in the pathogenesis of age-related macular degeneration.

S Beatty, H. Koh, M Phil … (2000)

Age-related macular degeneration (AMD) is the leading cause of blind registration in the developed world, and yet its pathogenesis remains poorly understood. Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates (ROI), has been implicated in many disease processes, especially age-related disorders. ROIs include free radicals, hydrogen peroxide, and singlet oxygen, and they are often the byproducts of oxygen metabolism. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, its high proportion of polyunsaturated fatty acids, and its exposure to visible light. In vitro studies have consistently shown that photochemical retinal injury is attributable to oxidative stress and that the antioxidant vitamins A, C, and E protect against this type of injury. Furthermore, there is strong evidence suggesting that lipofuscin is derived, at least in part, from oxidatively damaged photoreceptor outer segments and that it is itself a photoreactive substance. However, the relationships between dietary and serum levels of the antioxidant vitamins and age-related macular disease are less clear, although a protective effect of high plasma concentrations of alpha-tocopherol has been convincingly demonstrated. Macular pigment is also believed to limit retinal oxidative damage by absorbing incoming blue light and/or quenching ROIs. Many putative risk-factors for AMD have been linked to a lack of macular pigment, including female gender, lens density, tobacco use, light iris color, and reduced visual sensitivity. Moreover, the Eye Disease Case-Control Study found that high plasma levels of lutein and zeaxanthin were associated with reduced risk of neovascular AMD. The concept that AMD can be attributed to cumulative oxidative stress is enticing, but remains unproven. With a view to reducing oxidative damage, the effect of nutritional antioxidant supplements on the onset and natural course of age-related macular disease is currently being evaluated.

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Heinz Wässle (2004)

Our eyes send different 'images' of the outside world to the brain - an image of contours (line drawing), a colour image (watercolour painting) or an image of moving objects (movie). This is commonly referred to as parallel processing, and starts as early as the first synapse of the retina, the cone pedicle. Here, the molecular composition of the transmitter receptors of the postsynaptic neurons defines which images are transferred to the inner retina. Within the second synaptic layer - the inner plexiform layer - circuits that involve complex inhibitory and excitatory interactions represent filters that select 'what the eye tells the brain'.

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A Boulares, A G Yakovlev, V Ivanova … (1999)

An early transient burst of poly(ADP-ribosyl)ation of nuclear proteins was recently shown to be required for apoptosis to proceed in various cell lines (Simbulan-Rosenthal, C., Rosenthal, D., Iyer, S., Boulares, H., and Smulson, M. (1998) J. Biol. Chem. 273, 13703-13712) followed by cleavage of poly(ADP-ribose) polymerase (PARP), catalyzed by caspase-3. This inactivation of PARP has been proposed to prevent depletion of NAD (a PARP substrate) and ATP, which are thought to be required for later events in apoptosis. The role of PARP cleavage in apoptosis has now been investigated in human osteosarcoma cells and PARP -/- fibroblasts stably transfected with a vector encoding a caspase-3-resistant PARP mutant. Expression of this mutant PARP increased the rate of staurosporine and tumor necrosis factor-alpha-induced apoptosis, at least in part by reducing the time interval required for the onset of caspase-3 activation and internucleosomal DNA fragmentation, as well as the generation of 50-kilobase pair DNA breaks, thought to be associated with early chromatin unfolding. Overexpression of wild-type PARP in osteosarcoma cells also accelerated the apoptotic process, although not to the same extent as that apparent in cells expressing the mutant PARP. These effects of the mutant and wild-type enzymes might be due to the early and transient poly(ADP-ribose) synthesis in response to DNA breaks, and the accompanying depletion of NAD apparent in the transfected cells. The accelerated NAD depletion did not seem to interfere with the later stages of apoptosis. These results indicate that PARP activation and subsequent cleavage have active and complex roles in apoptosis.

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Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group

ISSN (Electronic): 2045-2322

Publication date (Electronic): 20 April 2017

Publication date Collection: 2017

Volume: 7

Electronic Location Identifier: 46449

Affiliations

[1 ]Natural Products Research Center, Korea Institute of Science and Technology (KIST) , Gangneung 25451, Republic of Korea

[2 ]Department of Biological Chemistry, Korea University of Science and Technology (UST) , Daejeon 34113, Republic of Korea

[3 ]Department of Biological Sciences, Pusan National University , Busan 46241, Republic of Korea

Author notes

[a ] tjkim77@ 123456pusan.ac.kr

[b ] shjung@ 123456kist.re.kr

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Publisher Item ID: srep46449

DOI: 10.1038/srep46449

PMC ID: 5397840

PubMed ID: 28425487

SO-VID: aaf8c34c-8fc2-4934-ae9f-6ce719fdd99a

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Persimmon Leaves ( Diospyros kaki) Extract Protects Optic Nerve Crush-Induced Retinal Degeneration

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Most cited references 57

The role of oxidative stress in the pathogenesis of age-related macular degeneration.

Parallel processing in the mammalian retina.

Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells.

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