Gene therapy for ocular diseases
Open accessAbstract
The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.
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AAVs generate relatively mild innate and adaptive immune responses, which allow for stable long-term transgene expression.
“Unlike adenoviruses, AAVs generate relatively mild innate and adaptive immune responses, which allow for stable long-term transgene expression.”
From Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses (2022) · cites this paper as [15]
The Ocular Gene Transfer Methods section says AAV vectors typically elicit minimal immune responses and allow stable, long-term transgene expression, while adenoviral vectors elicit robust immune responses that limit expression. It does not distinguish AAV’s innate from adaptive immune responses, so that specificity is not established by our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe small size, accessibility, confined structure, and immune-privileged status of the eye make it an ideal target for gene therapy.
“The small size, accessibility, confined structure, and immune-privileged status of the eye [74, 75], make it an ideal target for gene therapy”
From The economic impact of retinal diseases for which gene therapy is emerging: a systematic literature review (2025) · cites this paper as [74]
The Abstract (page unavailable) describes the eye as accessible, compartmentalised and immune-privileged, and says these features offer advantages for gene therapy. It does not identify the eye’s small size as one of those advantages. (LLM, conf=0.87)
Experimental — accuracy not yet measuredLonger-acting treatments such as gene therapy are sought to address the absences and inadequacies of currently available treatments in retinal diseases.
“To address these absences and inadequacies of currently available treatments in retinal diseases, longer-acting treatments such as gene therapy, are sought [74].”
From The economic impact of retinal diseases for which gene therapy is emerging: a systematic literature review (2025) · cites this paper as [74]
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Gene Therapy Targeting Glaucoma: Where Are We?
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AAV5-mediated sFLT01 gene therapy arrests retinal lesions in Ccl2−/−/Cx3cr1−/− mice
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Treatment of ocular disorders by gene therapy
Solinís, M. Á., del Pozo-Rodríguez, A., Apaolaza, P. S., & Rodríguez-Gascón, A. (2015) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2014.12.022 · Cited by 88 · see citing works
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“14,25,26 29 Independent of the route of administration (subretinal, intravitreal, or suprachoroidal), a dose-dependent in fl ammatory reaction has been noted in nearly all ocular gene therapies.”
BackgroundOcular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses
Ghoraba, H. H., Akhavanrezayat, A., Karaca, I., Yavari, N., Lajevardi, S., Hwang, J., Regenold, J., Matsumiya, W., Pham, B., Zaidi, M., et al. (2022) · Clinical Ophthalmology · doi:10.2147/opth.s364200 · Cited by 76 · see citing works
“Similar to adenovirus, AAVs can also infect dividing and non-dividing cells.(15,16) AAVs’ limited capacity to carry large-sized genetic material restricts their use in gene delivery for some diseases that are coded by large genes such as Usher syndrome.”
BackgroundAL Qtaish, N., Gallego, I., Villate-Beitia, I., Sainz-Ramos, M., López-Méndez, T. B., Grijalvo, S., Eritja, R., Soto-Sánchez, C., Martínez-Navarrete, G., Fernández, E., et al. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12030198 · Cited by 57 · see citing works
Naik, S., Shreya, A. B., Raychaudhuri, R., Pandey, A., Lewis, S. A., Hazarika, M., Bhandary, S. V., Rao, B. S. S., & Mutalik, S. (2021) · Life Sciences · doi:10.1016/j.lfs.2020.118712 · Cited by 33 · see citing works
Willmington, C., Kirby, A., & Murphy, A. (2025) · Health Economics Review · doi:10.1186/s13561-025-00707-7
“The small size, accessibility, confined structure, and immune-privileged status of the eye [74, 75], make it an ideal target for gene therapy, which in turn is less likely to cause excessive inflammatory and immune responses when delivered to this organ [76].”
- Authors
- Liu, M. M., Tuo, J., & Chan, C.-C.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Chan, C.-C.
- ORCID
- Venue
- British Journal of Ophthalmology
- Publisher
- BMJ
- Published
- 2010-08-23
- Volume
- 95
- Issue
- 5
- Pages
- 604-612
- ISSN
- 0007-1161 (ISSN-L)
- PMC
- PMC3154727
- OpenAlex
- W2114564223
- Cited by
- 82
- References
- 104
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 6 · 2015: 4 · 2014: 6 · 2013: 5 · 2012: 11
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (ZIAEY000222, T32EY007143)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- ocular gene therapy, gene delivery vectors, adeno-associated virus vectors, lentiviral vectors, retinal disease, retinitis pigmentosa, retinoschisis, Stargardt disease, age-related macular degeneration, uveitis, glaucoma, Leber congenital amaurosis, gene silencing, gene replacement
- MeSH terms
- Animals, Eye Diseases, Humans, Retinal Diseases, Genetic Therapy, Ocular Motility Disorders, Gene Transfer Techniques
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