Abstract
Aging is a risk factor for multiple retinal degeneration diseases. Entraining brain gamma oscillations with gamma-flicker light (γFL) has been confirmed to coordinate pathological changes in several Alzheimer’s disease mouse models and aged mice. However, the direct effect of γFL on retinal aging remains unknown. We assessed retinal senescence-associated beta-galactosidase (β-gal) and autofluorescence in 20-month-old mice and found reduced β-gal-positive cells in the inner retina and diminished lipofuscin accumulation around retinal vessels after 6 days of γFL. In immunofluorescence, γFL was further demonstrated to ameliorate aging-related retinal changes, including a decline in microtubule-associated protein 1 light chain 3 beta expression, an increase in complement C3 activity, and an imbalance between the anti-oxidant factor catalase and pro-oxidant factor carboxymethyl lysine. Moreover, we found that γFL can increase the expression of activating transcription factor 4 (ATF4) in the inner retina, while revealing a decrease of ATF4 expression in the inner retina and positive expression in the outer segment of photoreceptor and RPE layer for aged mice. Western blotting was then used to confirm the immunofluorescence results. After mRNA sequencing (NCBI Sequence Read Archive database: PRJNA748184), we found several main mechanistic clues, including mitochondrial function and chaperone-mediated protein folding. Furthermore, we extended γFL to aged Apoe−/− mice and showed that 1-m γFL treatment even improved the structures of retinal-pigment-epithelium basal infolding and Bruch’s membrane. Overall, γFL can orchestrate various pathological characteristics of retinal aging in mice and might be a noninvasive, convenient, and tissue-specific therapeutic strategy for retinal aging.
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Data Availability
Raw data of RNA sequencing were deposited in NCBI Sequence Read Archive database (PRJNA748184). All other data generated or used during the study appear in the submitted article.
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We thank Jimmy for optimizing the electric circuit.
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This work was supported by (1) National Natural Science Foundation of China (No. 32061160469); (2) the Fundamental Research Funds for the Central Universities of Central South University (No. 2019zzts368); (3) Research Grant of Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University (No. ZSYX-M-2019-00010); and (4) The Hong Kong Polytechnic University Joint Supervision Scheme with the Chinese Mainland, Taiwan and Macao Universities (No. G-SB1A).
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JSC, SBT, and BL designed the study. WS carried out the major experiment work. DL helped manage aged WT and Apoe−/− mice. ZKC helped analyze RNA sequencing data. YNW helped perform RT-qPCR. WS wrote the manuscript; JSC and SBT revised the manuscript.
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Sheng, W., Lv, D., Cui, ZK. et al. Tissue-Specific Gamma-Flicker Light Noninvasively Ameliorates Retinal Aging. Cell Mol Neurobiol 42, 2893–2907 (2022). https://doi.org/10.1007/s10571-021-01160-w
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DOI: https://doi.org/10.1007/s10571-021-01160-w