The DOI matches its Crossref record; 229 of the 243 references it cites were found in a registry or an index.
Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy
Open accessAbstract
Leber congenital amaurosis (LCA) is a rare hereditary retinal degeneration caused by mutations in more than a dozen genes. RPE65, one of these mutated genes, is highly expressed in the retinal pigment epithelium where it encodes the retinoid isomerase enzyme essential for the production of chromophore which forms the visual pigment in rod and cone photoreceptors of the retina. Congenital loss of chromophore production due to RPE65-deficiency together with progressive photoreceptor degeneration cause severe and progressive loss of vision. RPE65-associated LCA recently gained recognition outside of specialty ophthalmic circles due to early success achieved by three clinical trials of gene therapy using recombinant adeno-associated virus (AAV) vectors. The trials were built on multitude of basic, pre-clinical and clinical research defining the pathophysiology of the disease in human subjects and animal models, and demonstrating the proof-of-concept of gene (augmentation) therapy. Substantial gains in visual function of clinical trial participants provided evidence for physiologically relevant biological activity resulting from a newly introduced gene. This article reviews the current knowledge on retinal degeneration and visual dysfunction in animal models and human patients with RPE65 disease, and examines the consequences of gene therapy in terms of improvement of vision reported.
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“For RPE65 the severity of disease has been associated with the degree of residual enzymatic activity.274,281,557”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [274]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“RPE65 catalyses the conversion of all-trans-retinyl ester to 11-cis-retinol, allowing it to be reused in phototransduction and preventing its conversion to potentially toxic molecules.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [109]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In addition, retinyl esters accumulate in the RPE, leading to its damage [7,108,109,110].”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [109]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“The pathogenesis, therefore, combines local vitamin A deficiency and its impaired metabolism, which leads to the formation of toxic byproducts.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [109]
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In the citing paper
“Pathogenic variants in RPE65 result in 11-cis-retinol and subsequently 11-cis-retinal deficiency, which essentially stops the visual cycle.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [109]
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In the citing paper
“Dysfunction of such processes as phagocytosis, lysosomal degradation, and removal of waste products by the RPE can lead to severe retinopathies, including age-related macular degeneration (AMD).”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [274]
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Cites
Huang, D., Swanson, E. A., Lin, C. P., Schuman, J. S., Stinson, W. G., Chang, W., Hee, M. R., Flotte, T., Gregory, K. W., Puliafito, C. A., et al. (1991) · Science · doi:10.1126/science.1957169 · Cited by 14,001
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Human photoreceptor topography
Curcio, C. A., Sloan, K. R., Kalina, R. E., & Hendrickson, A. E. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.902920402 · Cited by 2,894
New Visual Acuity Charts for Clinical Research
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Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802315 · Cited by 2,145
Experience-dependent structural synaptic plasticity in the mammalian brain
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Effect of gene therapy on visual function in Leber’s congenital amaurosis
Bainbridge, J. W. B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802268 · Cited by 1,924
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The Major Cell Populations of the Mouse Retina
Jeon, C.-J., Strettoi, E., & Masland, R. H. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-21-08936.1998 · Cited by 1,429
Hattar, S., Lucas, R. J., Mrosovsky, N., Thompson, S., Douglas, R. H., Hankins, M. W., Lem, J., Biel, M., Hofmann, F., Foster, R. G., et al. (2003) · Nature · doi:10.1038/nature01761 · Cited by 1,245
Research works printed but not linked: 1
- Gal, 1998, Mutation spectrum of RPE65 in autosomal recessive childhood-onset severe retinal dystrophy, Investig. Ophthalmol. Vis. Sci., 39, S901
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Current clinical applications of in vivo gene therapy with AAVs
Mendell, J. R., Al-Zaidy, S. A., Rodino-Klapac, L. R., Goodspeed, K., Gray, S. J., Kay, C. N., Boye, S. L., Boye, S. E., George, L. A., Salabarria, S., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2020.12.007 · Cited by 743
Engineered Virus-like Particles for Efficient in Vivo Delivery of Therapeutic Proteins
Banskota, S., Raguram, A., Suh, S., Du, S. W., Davis, J. R., Choi, E. H., Wang, X., Nielsen, S. C., Newby, G. A., Randolph, P. B., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.021 · Cited by 668
Jacobson, S. G. (2012) · Archives of Ophthalmology · doi:10.1001/archophthalmol.2011.298 · Cited by 639
High, K. A., & Roncarolo, M. G. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1706910 · Cited by 555
Cideciyan, A. V., Jacobson, S. G., Beltran, W. A., Sumaroka, A., Świder, M., Iwabe, S., Román, A. J., Olivares, M. B., Schwartz, S., Komáromy, A. M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218933110 · Cited by 441
Self-citation
Metadata
- Authors
- Cideciyan, A. V.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Cideciyan, Artur V.
- ORCID
- Cideciyan, Artur V.
- Venue
- Progress in Retinal and Eye Research
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 29
- Issue
- 5
- Pages
- 398-427
- ISSN
- 1350-9462 (ISSN-L)
- PMC
- PMC2903652
- OpenAlex
- W1970654757
- Cited by
- 256
- References
- 243
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 13 · 2023: 11 · 2022: 13 · 2021: 18 · 2020: 14 · 2019: 19 · 2018: 10 · 2017: 12 · 2016: 11 · 2015: 21 · 2014: 18 · 2013: 22 · 2012: 23
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Progress in Retinal and Eye Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (U10EY017280, R01EY013203)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- Leber congenital amaurosis, RPE65 mutations, gene therapy, recombinant adeno-associated virus vectors, retinal pigment epithelium, photoreceptor degeneration, inherited retinal degeneration, animal models, visual function outcomes
- MeSH terms
- Retinoid Isomerohydrolase, Animals, Carrier Proteins, DNA, Eye Proteins, Humans, Mutation, Genetic Therapy, cis-trans-Isomerases, Leber Congenital Amaurosis
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