Aakanksha Pathania, B.Optom


The eye is a complex sensory organ that evolved to promote our survival and appreciation of beauty. (1) Retinal genetic defects cause sight-impairing and blinding disorders that lead to degeneration and death of visual cells. (2)  

It is imperative to understand that genetic diseases were once considered untreatable. However, with recent advancements in medical technology, we must acknowledge that there is now a ray of hope for those affected. (3) Ocular gene therapies can greatly enhance the lives of those with inherited retinal disease. (1)

The term gene therapy typically involves replacing a mutated gene in a targeted population of cells with a normal, functional copy delivered by a vector. (4,5)

Gene therapy can treat and cure inherited disorders and disease-causing mutations, offering hope to millions. (3,6) Gene therapy has come a long way. Before 1990, there were few treatments for retinal genetic diseases. Today, with over 1000 clinical trials (>30 for ocular disease), gene therapy is a beacon of hope for millions. The history of gene therapy is complex, but its advances are impressive. (3)

The retina is an ideal target for gene therapy due to its enclosed, immune-privileged site protected by the blood-retina barrier. Additionally, only small amounts of the vector are needed to treat retinal diseases because of the retina’s small size and lack of cellular proliferation in adulthood. (1,3)     

There are 4 major approaches to gene therapy, mentioned below:

  1. Gene replacement/augmentation:  Gene replacement therapy entails providing a functional copy of a defective gene to boost the production of a functional protein, primarily for monogenic recessive inherited diseases. (3) 

    However, it may not be suitable for all gene mutations. Moreover, its widespread implementation can be costly and limit patient access.

  2. Gene Silencing:  With small interfering RNA or microRNA that targets vascular endothelial growth factor, is currently in development for the treatment of age-related macular degeneration, glaucoma, and several other ocular diseases. (3)
  3. Gene Editing: Gene editing corrects mutations in genes or reduces mutated protein expression to modify disease, but faces challenges like traditional gene therapy, especially the complexity of diseases involving multiple genes. (3)
  4. Modifier Gene Therapy: Modifier gene therapies are increasingly used for systemic diseases, targeting pathways adjacent to multiple faulty genes without a genetic diagnosis. Nonetheless, pinpointing modifier genes for a particular disease phenotype can be costly and challenging. (3)

Challenges of Gene Therapy:

While the retina’s immune privilege makes it an excellent candidate for gene therapies, it also presents challenges like identifying the disease-causing gene or mutation, ensuring targeted delivery, determining the appropriate administration route, assessing feasibility in the clinic, and managing potential immune responses that could harm the delicate tissue. (4,5)


Gene therapy is advancing as a treatment for previously untreatable forms of retinal blindness. Although the field is young, the enthusiasm from both the scientific community and patient advocacy groups is invigorating. (2)

A crucial aspect of future gene therapy development is devising ways to treat genetic diseases without a specific genetic diagnosis or to target multiple mutations with a single product. This approach would tackle two ongoing challenges in gene therapy: the high production costs and the necessity of identifying the genetic cause of a disease on an individual basis. (3)



  1. Boye, S. E., Boye, S. L., Lewin, A. S., & Hauswirth, W. W. (2013). A comprehensive review of retinal gene therapy. Molecular therapy21(3), 509-519.
  2. Concepts and Strategies in Retinal Gene Therapy, cited from [Internet][April 14] Available from: https://iovs.arvojournals.org/article.aspx?articleid=2659572#173899463
  3. Gene Therapy for Retinal Degenerative Diseases: Progress, Challenges, and Future Directions, cited from [Internet][April,14] Available from: https://iovs.arvojournals.org/article.aspx?articleid=2791262
  4. Gene Therapy for Inherited Retinal Disease, cited from[Internet][April,14] Available from: https://www.reviewofophthalmology.com/article/gene-therapy-for-inherited-retinal-disease
  5. Samiy, N. (2014). Gene therapy for retinal diseases. Journal of ophthalmic & vision research9(4), 506.
  6. Lipinski, D. M., Thake, M., & MacLaren, R. E. (2013). Clinical applications of retinal gene therapy. Progress in retinal and eye research32, 22-47.