TY - JOUR
T1 - Tissue-Specific Gamma-Flicker Light Noninvasively Ameliorates Retinal Aging
AU - Sheng, Wang
AU - Lv, Da
AU - Cui, Ze-Kai
AU - Wang, Yi-Ni
AU - Lin, Bin
AU - Tang, Shi-Bo
AU - Chen, Jian-Su
N1 - Funding Information:
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).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/10/26
Y1 - 2021/10/26
N2 - 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.
AB - 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.
KW - Phototherapy
KW - Retina
KW - Aging
KW - Mitochondrial disorders
KW - Molecular chaperones
UR - http://www.scopus.com/inward/record.url?scp=85118161944&partnerID=8YFLogxK
U2 - 10.1007/s10571-021-01160-w
DO - 10.1007/s10571-021-01160-w
M3 - Journal article
SN - 1573-6830
JO - Cellular and Molecular Neurobiology
JF - Cellular and Molecular Neurobiology
ER -