Small interfering RNAs (siRNAs) based gene silencing strategies for the treatment of glaucoma: Recent advancements and future perspectives

Life Sci. 2021 Jan 1:264:118712. doi: 10.1016/j.lfs.2020.118712. Epub 2020 Nov 4.

Abstract

RNA-interference-based mechanisms, especially the use of small interfering RNAs (siRNAs), have been under investigation for the treatment of several ailments and have shown promising results for ocular diseases including glaucoma. The eye, being a confined compartment, serves as a good target for the delivery of siRNAs. This review focuses on siRNA-based strategies for gene silencing to treat glaucoma. We have discussed the ocular structures and barriers to gene therapy (tear film, corneal, conjunctival, vitreous, and blood ocular barriers), methods of administration for ocular gene delivery (topical instillation, periocular, intracameral, intravitreal, subretinal, and suprachoroidal routes) and various viral and non-viral vectors in siRNA-based therapy for glaucoma. The components and mechanism of siRNA-based gene silencing have been mentioned briefly followed by the basic strategies and challenges faced during siRNA therapeutics development. We have emphasized different therapeutic targets for glaucoma which have been under research by scientists and the current siRNA-based drugs used in glaucoma treatment. We also mention briefly strategies for siRNA-based treatment after glaucoma surgery.

Keywords: Gene silencing; Glaucoma; RNA interference; siRNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Eye / pathology
  • Gene Silencing*
  • Gene Transfer Techniques
  • Genetic Therapy
  • Glaucoma / genetics*
  • Glaucoma / therapy*
  • Humans
  • RNA, Small Interfering / metabolism*

Substances

  • RNA, Small Interfering