TY - JOUR
T1 - Targeting the integrated stress response in ophthalmology
AU - Chu, Hsiao Sang
AU - Peterson, Cornelia
AU - Jun, Albert
AU - Foster, James
N1 - Funding Information:
This research was funded through a kind donation from the Division of Cornea and Anterior segment (Wilmer Eye Institute) - JF, The Research to Prevent Blindness Unrestricted Grant (Wilmer Eye institute)–JF; NIH T32 OD011089 (PI: Mankowski) - CP; National Taiwan University Hospital Research Grant 108-M4386 - HSC.
Publisher Copyright:
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2021
Y1 - 2021
N2 - Purpose: To summarize the Integrated Stress Response (ISR) in the context of ophthalmology, with special interest on the cornea and anterior segment. Results: The ISR is a powerful and conserved signaling pathway that allows for cells to respond to a diverse array of both intracellular and extracellular stressors. The pathway is classically responsible for coordination of the cellular response to amino acid starvation, ultraviolet light, heme dysregulation, viral infection, and unfolded protein. Under normal circumstances, it is considered pro-survival and a necessary mechanism through which protein translation is controlled. However, in cases of severe or prolonged stress the pathway can promote apoptosis, and loss of normal cellular phenotype. The activation of this pathway culminates in the global inhibition of cap-dependent protein translation and the canonical expression of the activating transcription factor 4 (ATF4). Conclusion:The eye is uniquely exposed to ISR responsive stressors due to its environmental exposure and relative isolation from the circulatory system which are necessary for its function. We will discuss how this pathway is critical for the proper function of the tissue, its role in development, as well as how targeting of the pathway could alleviate key aspects of diverse ophthalmic diseases.
AB - Purpose: To summarize the Integrated Stress Response (ISR) in the context of ophthalmology, with special interest on the cornea and anterior segment. Results: The ISR is a powerful and conserved signaling pathway that allows for cells to respond to a diverse array of both intracellular and extracellular stressors. The pathway is classically responsible for coordination of the cellular response to amino acid starvation, ultraviolet light, heme dysregulation, viral infection, and unfolded protein. Under normal circumstances, it is considered pro-survival and a necessary mechanism through which protein translation is controlled. However, in cases of severe or prolonged stress the pathway can promote apoptosis, and loss of normal cellular phenotype. The activation of this pathway culminates in the global inhibition of cap-dependent protein translation and the canonical expression of the activating transcription factor 4 (ATF4). Conclusion:The eye is uniquely exposed to ISR responsive stressors due to its environmental exposure and relative isolation from the circulatory system which are necessary for its function. We will discuss how this pathway is critical for the proper function of the tissue, its role in development, as well as how targeting of the pathway could alleviate key aspects of diverse ophthalmic diseases.
KW - ATF4
KW - ISR; isrib, cornea; eIF2
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U2 - 10.1080/02713683.2020.1867748
DO - 10.1080/02713683.2020.1867748
M3 - Review article
C2 - 33474991
AN - SCOPUS:85099993907
SN - 0271-3683
VL - 46
SP - 1075
EP - 1088
JO - Current Eye Research
JF - Current Eye Research
IS - 8
ER -