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Pyruvate Kinase 2, an Energy Metabolism Related Enzyme, May Have a Neuroprotective Function in Retinal Degeneration

Jiaming Zhou1, Per Ekström1

  • 1Ophthalmology, Department of Clinical Sciences, 5193Lund University, Lund, Sweden.

ASN Neuro
|February 17, 2023
PubMed

Insights

Pyruvate kinase 2 (PKM2) activation alleviates photoreceptor death in retinitis pigmentosa (RP) models. This finding suggests PKM2 is a potential therapeutic target for inherited retinal degeneration.

Area of Science:

  • Ophthalmology
  • Neuroscience
  • Molecular Biology

Background:

  • Retinitis pigmentosa (RP) is an inherited condition causing vision loss with limited treatment options.
  • The cyclic guanosine monophosphate (cGMP) pathway, including cGMP and cGMP-dependent protein kinase (PKG), is implicated in retinal degeneration.
  • Previous research identified cGMP-PKG-dependent genes relevant to RP.

Purpose of the Study:

  • To validate pyruvate kinase 2 (PKM2) as a cGMP-PKG-dependent gene in RP.
  • To investigate the role of PKM2 in photoreceptor survival during RP.
  • To explore PKM2 as a potential therapeutic target for RP.

Main Methods:

  • Utilized organotypic retinal explant cultures from RP mouse models (rd2 and rd10).
  • Pharmacologically modulated PKM2 activity using TEPP-46, a PKM2 activator.
  • Assessed photoreceptor survival and expression of PKM2 and glucose transporter-1 (Glut1).

Main Results:

  • PKM2 activation with TEPP-46 alleviated photoreceptor cell death in the rd10 RP mouse model.
  • Expression levels of PKM2 and its target Glut1 were altered in correlation with RP degeneration.
  • These findings support the involvement of PKM2 in photoreceptor well-being.

Conclusions:

  • PKM2 plays a role in photoreceptor survival in the context of retinitis pigmentosa.
  • Pharmacological activation of PKM2 shows therapeutic potential for RP.
  • PKM2 represents a promising novel molecular target for developing RP treatments.
Keywords:
PKM2TUNELcell deathorganotypic retinal explant cultureretinal degeneration

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