Review Article
Volume 12 Issue 5 - 2021
Recent Trends in Nano Delivery of siRNA to the Eye
Kaushal Divya1, Sneed KB2 and Pathak Yashwant V2,3*
1University of South Florida, Judy Genshaft Honors College, Tampa, Florida, USA
2College of Pharmacy, University of South Florida Health, Tampa, Florida, USA
2Adjunct Professor, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia
*Corresponding Author: Pathak Yashwant V, College of Pharmacy, University of South Florida Health, Tampa, Florida, USA.
Received: May 14, 2021; Published: July 31, 2021


The discovery of RNAi and the regulatory role that these small molecules play in the silencing of certain genes has captured the imagination of scientists and clinicians. siRNA delivery has been able to help address certain genetic mutations leading to altered gene expression or the accumulation of abnormal proteins- both of which can be associated with human diseases. Nanocarriers and siRNA can be used to create a targeted therapy that can aid in angiogenic ocular diseases such as age-related macular degeneration (AMD) and diabetic macular edema (DME). AMD and DME are ocular diseases that are due to the neovascularization in or underneath the retina- most often in the macula, the area of central high acuity vision. This can cause blurriness, distortion (metamorphopsia), and vision loss. Current treatments to decrease neovascularization are the application of anti-vascular endothelial growth factor (VEGF) antibodies which neutralize VEGF’s biological activity. Understanding both the siRNA biology of the eye along with nanoparticle delivery systems will help in improving target tissue delivery of these molecules and could make for a more clinically impactful therapy. Current studies have demonstrated the successful use of intravitreous Ets1 siRNA as a pro-angiogenic treatment in pro-inflammatory conditions. This improves the leakage and restricts the dysfunction of retinal epithelial (RPE) cells. Also, administering HuR siRNA intraocularly leads to decreases in the retinal HuR in diabetic rats which can be useful in diabetic retinopathy.

Keywords: RNAi; Age-Related Macular Degeneration (AMD); Diabetic Macular Edema (DME); Anti-Vascular Endothelial Growth Factor (VEGF); Retinal Epithelial (RPE)


  1. Kataki M., et al. “Nanoplatforms for Delivery of siRNA to the Eye”. Current Pharmaceutical Design31 (2015): 4587-4593.
  2. Park YG., et al. “New Approach of Anti-VEGF Agents for Age-Related Macular Degeneration”. Journal of Ophthalmology (2012): 1-7.
  3. Clearkin L., et al. “Anti-VEGF intervention in neovascular AMD: benefits and risks restated as natural frequencies”. BMJ Open Ophthalmology1 (2019).
  4. Tatiparti K., et al. “siRNA Delivery Strategies: A Comprehensive Review of Recent Developments”. Nanomaterials4 (2017): 77.
  5. Levanova A and Poranen MM. “RNA Interference as a Prospective Tool for the Control of Human Viral Infections”. Frontiers in Microbiology (2018): 9.
  6. Zhang R., et al. “Comprehensive Evolutionary Analysis of the Major RNA-Induced Silencing Complex Members”. Scientific Reports1 (2018).
  7. Fire A., et al. “Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans”. Nature6669 (1998): 806-811.
  8. Ray L. “Polymeric Nanoparticle-Based Drug/Gene Delivery for Lung Cancer”. Nanotechnology-Based Targeted Drug Delivery Systems for Lung Cancer (2019): 77-93.
  9. Dana H., et al. “Molecular Mechanisms and Biological Functions of siRNA”. International Journal of Biomedical Science: IJBS2 (2017): 48-57.
  10. Serrano-Sevilla I., et al. “Natural Polysaccharides for siRNA Delivery: Nanocarriers Based on Chitosan, Hyaluronic Acid, and Their Derivatives”. Molecules14 (2019): 2570.
  11. Konate K., et al. “Peptide-Based Nanoparticles to Rapidly and Efficiently “Wrap ’n Roll” siRNA into Cells”. Bioconjugate Chemistry3 (2018): 592-603.
  12. Kurrikoff K., et al. “Cell-Penetrating Peptides in Cancer Targeting”. Drug Delivery in Oncology (2011): 1187-1217.
  13. Beloqui A., et al. “Nanostructured lipid carriers as oral delivery systems for poorly soluble drugs”. Journal of Drug Delivery Science and Technology 42 (2017): 144-154.
  14. Ezzati Nazhad Dolatabadi J., et al. “Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs”. Advanced Pharmaceutical Bulletin2 (2015): 151-159.
  15. Thakur A., et al. “Strategies for ocular siRNA delivery: Potential and limitations of non-viral nanocarriers”. Journal of Biological Engineering1 (2012).
  16. Garba AO and Mousa SA. “Bevasiranib for the Treatment of Wet, Age-Related Macular Degeneration”. Ophthalmology and Eye Diseases (2010): 2.
  17. Nayerossadat N., et al. “Viral and nonviral delivery systems for gene delivery”. Advanced Biomedical Research1 (2012): 27.
  18. Landry B., et al. “Effective Non-Viral Delivery of siRNA to Acute Myeloid Leukemia Cells with Lipid-Substituted Polyethylenimines”. PLoS ONE8 (2012).
  19. Boulton M and Dayhaw-Barker P. “The role of the retinal pigment epithelium: Topographical variation and ageing changes”. Eye3 (2001): 384-389.
  20. Strauss O. “The Retinal Pigment Epithelium in Visual Function”. Physiological Reviews 3 (2005): 845-881.
  21. Simó R., et al. “The Retinal Pigment Epithelium: Something More than a Constituent of the Blood-Retinal Barrier—Implications for the Pathogenesis of Diabetic Retinopathy”. Journal of Biomedicine and Biotechnology (2010): 1-15.
  22. Bowmaker JK and Dartnall H J. “Visual pigments of rods and cones in a human retina”. Journal of Physiology 298 (1980): 501-511.
  23. Annaïg Hamon., et al. “Müller glial cell-dependent regeneration of the neural retina: An overview across vertebrate model systems”. Developmental Dynamics 7 (1980): 727-738.
  24. “The role of IL-7 in Immunity and Cancer”. Anticancer Research 3 (2017): 963-968.
  25. Solinís MÁ., et al. “Treatment of ocular disorders by gene therapy”. European Journal of Pharmaceutics and Biopharmaceutics 95 (2015): 331-342.
  26. Ambati J and Fowler BJ. “Mechanisms of Age-Related Macular Degeneration”. Neuron1 (2012): 26-39.
  27. Bahadorani S and Singer M. “Recent advances in the management and understanding of macular degeneration”. F1000 Research 6 (2017): 519.
  28. Yorston D. “Anti-VEGF drugs in the prevention of blindness”. Community Eye Health87 (2014): 44-46.
  29. Duh EJ., et al. “Diabetic retinopathy: current understanding, mechanisms, and treatment strategies”. JCI Insight14 (2017).
  30. Safi SZ., et al. “Molecular Mechanisms of Diabetic Retinopathy, General Preventive Strategies, and Novel Therapeutic Targets”. BioMed Research International (2014): 1-18.
  31. Lobo CL. “Alterations of the Blood-Retinal Barrier and Retinal Thickness in Preclinical Retinopathy in Subjects With Type 2 Diabetes”. Archives of Ophthalmology10 (2000): 1364.
  32. Hammes HP., et al. “Pericytes and the Pathogenesis of Diabetic Retinopathy”. Diabetes10 (2002): 3107-3112.
  33. Mirshahi A., et al. “Retinal Vascular Occlusions”. Deutsches Aerzteblatt Online (2008).
  34. Wang W and Lo A. “Diabetic Retinopathy: Pathophysiology and Treatments”. International Journal of Molecular Sciences6 (2018): 1816.
  35. Abràmoff MD., et al. “Automated Analysis of Retinal Images for Detection of Referable Diabetic Retinopathy”. JAMA Ophthalmology3 (2013): 351.
  36. Solomon SD., et al. “Diabetic Retinopathy: A Position Statement by the American Diabetes Association”. Diabetes Care3 (2017): 412-418.
  37. Semeraro F., et al. “Diabetic Retinopathy: Vascular and Inflammatory Disease”. Journal of Diabetes Research (2015): 1-16.
  38. Singh R., et al. “Diabetic retinopathy: an update”. Indian Journal of Ophthalmology3 (2008): 178-188.
  39. Llorián-Salvador M and González-Rodríguez S. “Painful Understanding of VEGF”. Frontiers in Pharmacology (2018): 9.
  40. Ferrara N. “Vascular Endothelial Growth Factor: Basic Science and Clinical Progress”. Endocrine Reviews4 (2004): 581-611.
  41. Holmes DIR and Zachary I. “The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease”. Genome Biology2 (2005): 209.
  42. Simons M., et al. “Mechanisms and regulation of endothelial VEGF receptor signalling”. Nature Reviews Molecular Cell Biology10 (2016): 611-625.
  43. Shibuya M. “Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies”. Genes and Cancer12 (2011): 1097-1105.
  44. Zhao L., et al. “Common Variant in VEGFA and Response to Anti-VEGF Therapy for Neovascular Age-Related Macular Degeneration”. Current Molecular Medicine6 (2013): 929-934.
  45. Ballmer-Hofer K. “Vascular Endothelial Growth Factor, from Basic Research to Clinical Applications”. International Journal of Molecular Sciences12 (2018): 3750.
  46. Hayreh SS., et al. “Incidence of Various Types of Retinal Vein Occlusion and Their Recurrence and Demographic Characteristics”. American Journal of Ophthalmology4 (1994): 429-441.
  47. Boyd SR. “Correlation of Increased Vascular Endothelial Growth Factor With Neovascularization and Permeability in Ischemic Central Vein Occlusion”. Archives of Ophthalmology12 (2002): 1644.
  48. Kumar S., et al. “Proteolytic Degradation and Inflammation Play Critical Roles in Polypoidal Choroidal Vasculopathy”. The American Journal of Pathology12 (2017): 2841-2857.
  49. Murakami Y., et al. “Photoreceptor cell death and rescue in retinal detachment and degenerations”. Progress in Retinal and Eye Research 37 (2013): 114-140.
  50. Cabral T., et al. “Retinal and choroidal angiogenesis: a review of new targets”. International Journal of Retina and Vitreous 3 (2017): 31.
  51. Yang S., et al. “Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review”. Drug Design, Development and Therapy 10 (2016): 1857-1867.
  52. Khurana RN. “Long-Term Management of Neovascular Age-Related Macular Degeneration: To Suspend or Not to Suspend?” Ophthalmology Retina 8 (2019): 621-622.
  53. Shin HJ., et al. “Intravitreal Anti–Vascular Endothelial Growth Factor Therapy and Retinal Nerve Fiber Layer Loss in Eyes With Age-Related Macular Degeneration: A Meta-Analysis”. Investigative Opthalmology and Visual Science 4 (2016): 1798.
  54. Gao Y., et al. “Research progress on siRNA delivery with nonviral carriers”. International Journal of Nanomedicine (2011): 1017.
  55. Rodriguez A., et al. “Non-Viral Delivery Systems in Gene Therapy”. Gene Therapy - Tools and Potential Applications (2013).
  56. Zhi D., et al. “Conjugates of small targeting molecules to non-viral vectors for the mediation of siRNA”. Acta Biomaterialia 36 (2016): 21-41.
  57. Ramamoorth M. “Non Viral Vectors in Gene Therapy- An Overview”. Journal Of Clinical And Diagnostic Research (2015).
  58. Tai W and Gao X. “Functional peptides for siRNA delivery”. Advanced Drug Delivery Reviews 110-111 (2017): 157-168.
  59. Feng W., et al. “Transcription Factor Avian Erythroblastosis Virus E26 Oncogen Homolog-1 Is a Novel Mediator of Renal Injury in Salt-Sensitive Hypertension”. Hypertension4 (2015): 813-820.
  60. Amadio M., et al. “Nanosystems based on siRNA silencing HuR expression counteract diabetic retinopathy in rat”. Pharmacological Research 111 (2016): 713-720.
  61. Green LC., et al. “Human antigen R as a therapeutic target in pathological cardiac hypertrophy”. JCI Insight4 (2019).
Citation: Kaushal Divya., et al. “Recent Trends in Nano Delivery of siRNA to the Eye”. EC Ophthalmology 12.8 (2021): 45-57.

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