Melatonin as the Possible Link Between Age-Related Retinal Degeneration and the Disrupted Circadian Rhythm in Elderly

2019 ◽  
pp. 45-49
Author(s):  
Nadezda A. Stepicheva ◽  
Joseph Weiss ◽  
Peng Shang ◽  
Meysam Yazdankhah ◽  
Sayan Ghosh ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Retinal Degeneration ◽  
Age Related

Effects of aging on entrainment and rate of resynchronization of circadian locomotor activity

1992 ◽  
Vol 263 (5) ◽  
pp. R1099-R1103 ◽  
Author(s):  
P. C. Zee ◽  
R. S. Rosenberg ◽  
F. W. Turek
Keyword(s):  
Circadian Rhythm ◽  
Locomotor Activity ◽  
Activity Rhythm ◽  
Phase Advance ◽  
Middle Aged ◽  
Age Related ◽  
Free Running ◽  
Effects Of Aging ◽  
Free Running Period ◽  
Related Phase

The phase angle of entrainment of the circadian rhythm of the locomotor activity rhythm to a light-dark (LD) cycle was examined in young (2-5 mo old) and middle-aged (13-16 mo old) hamsters. An age-related phase advance in the onset of locomotor activity relative to lights off was seen during stable entrainment to a 14:10-h LD cycle. In addition, the effects of age on the rate of reentrainment of the circadian rhythm of locomotor activity were examined by subjecting young and middle-aged hamsters to either an 8-h advance or delay shift of the LD cycle. Middle-aged hamsters resynchronized more rapidly after a phase advance of the LD cycle than did young hamsters, whereas young hamsters were able to phase delay more rapidly than middle-aged hamsters. The age-related phase advance of activity onset under entrained conditions, and the alteration of responses in middle-aged hamsters reentraining to a phase-shifted LD cycle, may be due to the shortening of the free-running period of the circadian rhythm of locomotor activity with advancing age that has previously been observed in this species.

scholarly journals Potential Treatment of Retinal Diseases with Iron Chelators

2018 ◽  
Vol 11 (4) ◽  
pp. 112 ◽  
Author(s):  
Wanting Shu ◽  
Joshua Dunaief
Keyword(s):  
Retinal Degeneration ◽  
Therapeutic Potential ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Hereditary Diseases ◽  
Iron Chelators ◽  
Excess Iron ◽  
Age Related

Iron is essential for life, while excess iron can be toxic. Iron generates hydroxyl radical, which is the most reactive free radical, causing oxidative stress. Since iron is absorbed through the diet but not excreted from the body, it accumulates with age in tissues, including the retina, consequently leading to age-related toxicity. This accumulation is further promoted by inflammation. Hereditary diseases such as aceruloplasminemia, Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration, and posterior column ataxia with retinitis pigmentosa involve retinal degeneration associated with iron dysregulation. In addition to hereditary causes, dietary or parenteral iron supplementation has been recently reported to elevate iron levels in the retinal pigment epithelium (RPE) and promote retinal degeneration. Ocular siderosis from intraocular foreign bodies or subretinal hemorrhage can also lead to retinopathy. Evidence from mice and humans suggests that iron toxicity may contribute to age-related macular degeneration pathogenesis. Iron chelators can protect photoreceptors and RPE in various mouse models. The therapeutic potential for iron chelators is under investigation.

Age-Related Modifications of Circadian Rhythm of Serum Leptin in Healthy Men

Gerontology ◽  
2002 ◽  
Vol 48 (5) ◽  
pp. 309-314 ◽  
Author(s):  
Zi-Yan Zhao ◽  
Yue-Rong Fu ◽  
Xin-Hua Li ◽  
Yu-Yang Li ◽  
André Bogdan ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Serum Leptin ◽  
Healthy Men ◽  
Age Related

scholarly journals Circadian Gating of Epithelial-to-Mesenchymal Transition in Breast Cancer Cells Via Melatonin-Regulation of GSK3β

2012 ◽  
Vol 26 (11) ◽  
pp. 1808-1820 ◽  
Author(s):  
Lulu Mao ◽  
Robert T. Dauchy ◽  
David E. Blask ◽  
Lauren M. Slakey ◽  
Shulin Xiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Circadian Rhythm ◽  
Sleep Disturbances ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Glycogen Synthase ◽  
Human Breast ◽  
Light At Night ◽  
Mesenchymal Transition ◽  
Age Related

Abstract Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer, but the underlying mechanisms are unknown. Employing a tissue-isolated human breast xenograft tumor nude rat model, we observed that glycogen synthase kinase 3β (GSK3β), an enzyme critical in metabolism and cell proliferation/survival, exhibits a circadian rhythm of phosphorylation in human breast tumors. Exposure to light-at-night suppresses the nocturnal pineal melatonin synthesis, disrupting the circadian rhythm of GSK3β phosphorylation. Melatonin activates GSK3β by inhibiting the serine-threonine kinase Akt phosphorylation, inducing β-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Thus, chronic circadian disruption by light-at-night via occupational exposure or age-related sleep disturbances may contribute to cancer incidence and the metastatic spread of breast cancer by inhibiting GSK3β activity and driving epithelial-to-mesenchymal transition in breast cancer patients.

Age-Related Circadian Rhythm of DHEAS Plasma Levels in Male Subjects

2001 ◽  
Vol 32 (3) ◽  
pp. 323-331
Author(s):  
Maria Teresa Guagnano ◽  
Adriana Del Ponte ◽  
Maria Rosaria Manigrasso ◽  
Daniele Merlitti ◽  
Valeria Pace-Palitti ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Plasma Levels ◽  
Age Related ◽  
Male Subjects

scholarly journals Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

2020 ◽  
Vol 21 (3) ◽  
pp. 704 ◽  
Author(s):  
Dmitry V. Chistyakov ◽  
Viktoriia E. Baksheeva ◽  
Veronika V. Tiulina ◽  
Sergei V. Goriainov ◽  
Nadezhda V. Azbukina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Aqueous Humor ◽  
Rabbit Model ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Cyclooxygenase Inhibitor ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Degenerative Diseases

Ocular inflammation contributes to the pathogenesis of blind-causing retinal degenerative diseases, such as age-related macular degeneration (AMD) or photic maculopathy. Here, we report on inflammatory mechanisms that are associated with retinal degeneration induced by bright visible light, which were revealed while using a rabbit model. Histologically and electrophysiologically noticeable degeneration of the retina is preceded and accompanied by oxidative stress and inflammation, as evidenced by granulocyte infiltration and edema in this tissue, as well as the upregulation of total protein, pro-inflammatory cytokines, and oxidative stress markers in aqueous humor (AH). Consistently, quantitative lipidomic studies of AH elucidated increase in the concentration of arachidonic (AA) and docosahexaenoic (DHA) acids and lyso-platelet activating factor (lyso-PAF), together with pronounced oxidative and inflammatory alterations in content of lipid mediators oxylipins. These alterations include long-term elevation of prostaglandins, which are synthesized from AA via cyclooxygenase-dependent pathways, as well as a short burst of linoleic acid derivatives that can be produced by both enzymatic and non-enzymatic free radical-dependent mechanisms. The upregulation of all oxylipins is inhibited by the premedication of the eyes while using mitochondria-targeted antioxidant SkQ1, whereas the accumulation of prostaglandins and lyso-PAF can be specifically suppressed by topical treatment with cyclooxygenase inhibitor Nepafenac. Interestingly, the most prominent antioxidant and anti-inflammatory benefits and overall retinal protective effects are achieved by simultaneous administrating of both drugs indicating their synergistic action. Taken together, these findings provide a rationale for using a combination of mitochondria-targeted antioxidant and cyclooxygenase inhibitor for the treatment of inflammatory components of retinal degenerative diseases.

scholarly journals Age-related disruptions of circadian rhythm and memory in the senescence-accelerated mouse (SAMP8)

AGE ◽  
2006 ◽  
Vol 28 (3) ◽  
pp. 283-296 ◽  
Author(s):  
Kevin C. H. Pang ◽  
Jonathan P. Miller ◽  
Ashley Fortress ◽  
J. Devin McAuley
Keyword(s):  
Circadian Rhythm ◽  
Age Related ◽  
Senescence Accelerated Mouse

scholarly journals Combination of Neuroprotective and Regenerative Agents for AGE-Induced Retinal Degeneration: In Vitro Study

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Guzel Bikbova ◽  
Toshiyuki Oshitari ◽  
Takayuki Baba ◽  
Shuichi Yamamoto
Keyword(s):  
Retinal Degeneration ◽  
Active Form ◽  
Collagen Gel ◽  
In Vitro Study ◽  
Sprague Dawley ◽  
Caspase 9 ◽  
Dapi Staining ◽  
Age Related ◽  
Retinal Explants

To determine the most effective combination of neuroprotective and regenerative agents for cultured retinal neurons from advanced glycation end products- (AGEs-) induced degeneration, retinal explants of 7 adult Sprague-Dawley rats were three-dimensionally cultured in collagen gel and incubated in serum-free media and in 7 media; namely, AGEs, AGEs + 100 μM citicoline, AGEs + 10 ng/mL NT-4, AGEs + 100 μM TUDCA, AGEs + 100 μM citicoline + TUDCA (doublet), and AGEs + 100 μM citicoline + TUDCA + 10 ng/mL NT-4 (triplet) were examined. The number of regenerating neurites was counted after 7 days of culture, followed by performing TUNEL and DAPI staining. The ratio of TUNEL-positive cells to the number of DAPI-stained nuclei was calculated. Immunohistochemical examinations for the active form of caspase-9 and JNK were performed. All of the neuroprotectants increased the number of neurites and decreased the number of TUNEL-positive cells. However, the number of neurites was significantly higher, and the number of TUNEL-positive cells and caspase-9- and JNK-immunopositive cells was fewer in the retinas incubated with the combined three agents. Combination solutions containing citicoline, TUDCA, and NT-4 should be considered for neuroprotective and regenerative therapy for AGE-related retinal degeneration.

scholarly journals Quantitative metabolomics of photoreceptor degeneration and the effects of stem cell-derived retinal pigment epithelium transplantation

2016 ◽  
Vol 374 (2079) ◽  
pp. 20150376 ◽  
Author(s):  
Junhua Wang ◽  
Peter D. Westenskow ◽  
Mingliang Fang ◽  
Martin Friedlander ◽  
Gary Siuzdak
Keyword(s):  
Stem Cell ◽  
Retinal Pigment Epithelium ◽  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Photoreceptor Degeneration ◽  
Quantitative Metabolomics ◽  
Fatty Acid Amides ◽  
Age Related

Photoreceptor degeneration is characteristic of vision-threatening diseases including age-related macular degeneration. Photoreceptors are metabolically demanding cells in the retina, but specific details about their metabolic behaviours are unresolved. The quantitative metabolomics of retinal degeneration could provide valuable insights and inform future therapies. Here, we determined the metabolomic ‘fingerprint’ of healthy and dystrophic retinas in rat models using optimized metabolite extraction techniques. A number of classes of metabolites were consistently dysregulated during degeneration: vitamin A analogues, fatty acid amides, long-chain polyunsaturated fatty acids, acyl carnitines and several phospholipid species. For the first time, a distinct temporal trend of several important metabolites including DHA (4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid), all- trans -retinal and its toxic end-product N -retinyl- N -retinylidene-ethanolamine were observed between healthy and dystrophic retinas. In this study, metabolomics was further used to determine the temporal effects of the therapeutic intervention of grafting stem cell-derived retinal pigment epithelium (RPE) in dystrophic retinas, which significantly prevented photoreceptor atrophy in our previous studies. The result revealed that lipid levels such as phosphatidylethanolamine in eyes were restored in those animals receiving the RPE grafts. In conclusion, this study provides insight into the metabolomics of retinal degeneration, and further understanding of the efficacy of RPE transplantation. This article is part of the themed issue ‘Quantitative mass spectrometry’.

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