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Calpains as mechanistic drivers and therapeutic targets for ocular disease

Jennifer T Vu1, Elena Wang1, Jolan Wu1

  • 1Molecular Surgery Laboratory, Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, CA 94304, USA.

Trends in Molecular Medicine
|May 31, 2022
PubMed

Insights

Calpain dysregulation drives ophthalmic neurodegenerative diseases. Targeting these calcium-dependent proteases in the eye offers unique therapeutic advantages for treating eye conditions and potentially other diseases.

Area of Science:

  • Ophthalmology
  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Ophthalmic neurodegenerative diseases share common molecular pathologies linked to calpain dysregulation.
  • Calpains are calcium-dependent proteases implicated in cellular death and inflammation when hyperactivated.
  • The eye presents unique advantages for developing and testing targeted calpain inhibitors compared to other organs.

Purpose of the Study:

  • To review the structural mechanisms of calpain activation.
  • To examine cellular expression patterns of calpains in the eye.
  • To highlight in vivo models linking calpain hyperactivity to retinal and developmental diseases.

Main Methods:

  • Literature review focusing on calpain structure, function, and disease association.
  • Analysis of cellular expression data for calpains in ocular tissues.
  • Evaluation of preclinical models of calpain-mediated eye diseases.

Main Results:

  • Calpain hyperactivation is a unifying factor in various ophthalmic neurodegenerative diseases.
  • The eye's accessibility facilitates diverse therapeutic strategies, including small molecules, peptides, proteins, implants, and gene therapies.
  • Understanding calpain mechanisms in the eye can inform broader therapeutic development.

Conclusions:

  • Targeting calpain dysregulation in the eye is a promising therapeutic avenue.
  • The eye serves as an advantageous model for developing and testing novel calpain inhibitors.
  • Advances in treating calpain-mediated eye diseases may accelerate strategies for other organ systems.
Keywords:
blindnesscalcium dysregulationcalpainretinatherapeutics

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