Role of small interfering RNA (siRNA) in targeting ocular neovascularization: A review

Exp Eye Res. 2021 Jan:202:108329. doi: 10.1016/j.exer.2020.108329. Epub 2020 Oct 23.

Abstract

Ocular neovascularization (NV) plays a central role in the pathogenesis of various ocular diseases including diabetic retinopathy, age-related macular degeneration, retinoblastoma, retinitis pigmentosa and may lead to loss of vision if not controlled in time. Several clinical trials elucidate the central role of vascular endothelial growth factor (VEGF) in the pathogenesis of the ocular neovascularization. The advent and extensive use of ocular anti-VEGF therapy heralded a new age in the treatment of retinal vascular and exudative diseases. RNA interference (RNAi) can be used to inhibit the in-vitro and in-vivo expression of specific genes and thus provides an extremely useful method for investigating gene activity with minimal toxicity. siRNA targeting VEGF overcomes many drawbacks associated with the conventional treatment available for the treatment of ocular neovascularization. However, delivery methods that protect the siRNA against degradation and are appropriate for long-term care will help increase the effectiveness of RNAi-based anti-VEGF ocular therapies. Several nanotechnology approaches have been explored by formulation scientists for delivery of siRNA to the eye; targeting particularly VEGF for the treatment of NV. This review mainly focuses on current updates in various pre-clinical and clinical siRNA strategies for targeting VEGF involved in the development of ocular neovascularization.

Keywords: 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine; Cationic polymer; Chitosan; Ethylene glycol; Hyaluronic acid; Liposomes; Ocular cular siRNA delivery; Ocular neovascularization (NV); PEG2000 DSPE; Poly-l-lysine; Polyethylenimine; Polyplexes, Lipoplexes, siRNA formulations, Diabetic retinopathy, Age-related macular degeneration, Patents on siRNA against ocular NV, Clinical trials; PubChem CID 406952; PubChem CID 5962; PubChem CID: 162282; PubChem CID: 174; PubChem CID: 21896651; PubChem CID: 24847767; PubChem CID: 447078; PubChem CID: 9033; Small interfering RNA (siRNA); Vascular endothelial growth factor (VEGF); lysine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetic Retinopathy / genetics
  • Eye / blood supply*
  • Genetic Therapy / methods*
  • Humans
  • Neovascularization, Pathologic / therapy*
  • RNA Interference
  • RNA, Small Interfering / genetics*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • RNA, Small Interfering
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A