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Related Experiment Video

Updated: Sep 16, 2025

Organotypic Retinal Explant Cultures from Macaque Monkey
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Organotypic Retinal Explant Cultures from Macaque Monkey

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Calcium-dependent pathway as a primary cause of hypoxic RGC damage in monkey retinal explants.

Emi Nakajima1,2, Momoko Otsugu-Kobayashi3, Takatoshi Uchida1,2

  • 1Senju Laboratory of Ocular Sciences, Senju Pharmaceutical Corporation Limited, Portland, Oregon, United States of America.

Plos One
|July 11, 2025
PubMed
Summary
This summary is machine-generated.

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Calcium influx, not cathepsins, drives retinal ganglion cell (RGC) damage during hypoxia/reperfusion. Blocking calcium entry prevents RGC loss, highlighting its critical role in sight-threatening conditions like glaucoma.

Area of Science:

  • Ophthalmology and Visual Sciences
  • Neuroscience
  • Cellular and Molecular Biology

Background:

  • Retinal ganglion cell (RGC) loss is a key feature of glaucoma and retinopathy.
  • Previous research implicated calpains in hypoxia-induced RGC damage.
  • The role of calcium-independent proteases, like cathepsins, in this process remained unclear.

Purpose of the Study:

  • To investigate the involvement of cathepsins in RGC damage under hypoxia/reoxygenation.
  • To elucidate the specific role of calcium in hypoxia-induced RGC injury.

Main Methods:

  • Monkey retinal explants were subjected to hypoxia/reoxygenation.
  • Specific inhibitors for cathepsins and calpains were used.
  • Calcium chelators (BAPTA, BAPTA-AM) were employed to assess calcium's role.

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  • RGC damage was quantified using propidium iodide staining and α-spectrin breakdown product (SBDP150) analysis.
  • Main Results:

    • Cathepsin inhibitors did not protect RGCs from hypoxia/reoxygenation-induced damage.
    • Calcium chelators, particularly BAPTA, significantly inhibited RGC damage.
    • Calpain activation (increased SBDP150) was observed under hypoxia and was reduced by calcium chelation and calpain inhibitors.

    Conclusions:

    • Calcium-independent cathepsins are not involved in RGC damage during hypoxia/reperfusion.
    • Extracellular calcium influx is critical for inducing RGC damage.
    • Elevated intracellular calcium likely activates calpains, contributing to RGC degeneration, though other calcium-dependent pathways may also be involved.