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March 1, 2026Journal of Biological ChemistryOpen Access

Age-dependent induction of ER stress in retinal pigment epithelium impairs phagocytosis via ADAM17-dependent MERTK shedding

Hiroto Yasuda Shinsuke Nakamura Aimi Shirakawa Yoshiki Kuse Kazutoshi Mori Masamitsu Shimazawa

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Key Points

The research aims to understand how age-related ER stress affects phagocytic function in retinal pigment epithelium.
Examined RPE tissues from middle-aged mice and cultured RPE cells.
Measured ER stress marker proteins in RPE-choroid complex.
Induced ER stress pharmacologically using tunicamycin and observed effects on phagocytosis.
Used sodium 4-phenylbutyrate to alleviate ER stress effects.
Knocked down ADAM17 to study its role in phagocytosis impairment.
ER stress markers were significantly upregulated in 12-month-old mice RPE compared to younger mice.
Tunicamycin treatment reduced phagocytic activity and lysosomal function in cultured RPE cells.
Chemical chaperone treatment improved phagocytic dysfunction induced by ER stress.
ADAM17 activation linked to decreased MERTK levels and impaired POS internalization.

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Implication

Examines how ER stress affects phagocytic activity in retinal pigment epithelium, suggesting implications for retinal diseases.

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Cite This Study

Yasuda et al. (2026) studied this question.

synapsesocial.com/papers/69c37acab34aaaeb1a67caf8 https://doi.org/10.1016/j.jbc.2026.111397

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