Correcting visual loss by genetics and prosthetics
Open accessAbstract
Retinal degenerations account for the majority of untreatable causes of blindness. Advances in gene delivery vectors, CRISPR/Cas9-based gene editing systems, and electronic engineering have led to a wide range of strategies for correcting visual loss. Here, we provide an overview of retinal gene therapy, gene editing, optogenetics and retinal prostheses using examples from recent clinical trials and pre-clinical studies.
AI snapshot
Written from the paper’s full text.
TL;DR
This review surveys targeted genetic therapies (AAV gene replacement and CRISPR/Cas9 editing) and generic approaches (optogenetics and retinal prostheses) for retinal degeneration. It highlights clinical successes such as Luxturna and choroideremia/RPGR gene therapy alongside prosthetic devices that restore basic visual tasks in end-stage disease.
Key findings
- Luxturna (voretigene neparvovec) became the first FDA-approved gene therapy for RPE65-associated Leber congenital amaurosis, with phase I–III trials showing sustained improvements in low-luminance vision.
- A phase I/II choroideremia trial using AAV2-REP1 showed sustained preservation or improvement of visual acuity over 2 to 5 years; preliminary RPGR gene therapy results indicated reversal of visual field loss at the optimal therapeutic dose.
- Retinal prostheses enabled basic visual tasks: Argus II has a 60-electrode array spanning ~20 degrees, durability generally exceeding 5 years, and best reported grating visual acuity around 1.8 logMAR (6/379); Alpha AMS has a 1600 photodiode array spanning ~15 degrees and best documented grating visual acuity around 0.95 logMAR (6/60); a 22-electrode suprachoroidal device achieved Landolt-C visual acuity around 2.62 logMAR (20/8397).
- AAV vectors have a cargo capacity of up to 4.7 kb, and over 200 retinal disease-causing genes have been mapped; approximately 50% of retinitis pigmentosa is autosomal dominant, with RHO mutations accounting for 30–40% of those cases.
Methods
- Narrative review; no primary data collection, systematic search, or meta-analysis is described.
- Synthesizes examples from recent clinical trials and pre-clinical studies of retinal gene therapy, gene editing, optogenetics, and retinal prostheses.
- No formal quantitative analysis or risk-of-bias assessment is reported.
Limitations
- Stated: AAV cargo capacity is limited to 4.7 kb, dual-vector gene therapy is intrinsically less efficient, intravitreal AAV is less effective in primates and high doses may increase intraocular inflammation risk, and gene editing requires further work on off-target effects, long-term clinical safety, and ethical implications.
- Stated: Clinical interpretation is challenging because in vivo transduction/expression levels are unknown in choroideremia, LHON outcomes are confounded by natural variability, wet AMD gene therapy has unclear advantage over standard anti-VEGF injections, and dry AMD complement factor I therapy remains to be seen.
- Evident: As a narrative review, it lacks systematic search methods, quantitative synthesis, and primary outcome data.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 37 cited sources checked · 0 supported · 0 flagged
- Premisereasoning
Fusing an inactive Cas9 to a transcriptional repressor can specifically knock down expression of a disease-causing gene without permanently changing the genome.
“Furthermore, modification of the CRISPR/Cas9 components, for instance by fusing an enzymatically inactive Cas9 endonuclease to a transcriptional repressor, could allow specific knockdown of the disease-causing gene expression without creating any permanent change to the genome.”
Quote in the paperNot a substantial claim - Premisecitation
Phase I-III trials of Luxturna consistently showed sustained improvements in low-light vision in patients who were otherwise blind.
“Phase I to III clinical trials for Luxturna have consistently demonstrated its ability to bring about sustained improvements in low luminance vision in otherwise blind patients [Maguire 2009; Bennett 2016; Russell 2017].”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationnone given
Gene replacement therapies are proving effective for several recessive inherited retinal dystrophies.
“While gene replacement therapies are proving efficacious for a number of recessive inherited retinal dystrophies”
Quote in the paperSubstantial claim - Premisecitation
AAV particles have a DNA packaging limit of about 4.7 kb, which must accommodate the therapeutic gene, regulatory sequences, and inverted terminal repeats.
“The recombinant AAV viral vector is a replication-incompetent viral particle consisting of an icosahedral protein capsid encasing a single-stranded DNA genome, which can be a maximum 4.7 kb including the coding gene of interest, transcriptional regulatory elements and inverted terminal repeats (Fig. 1) [Samulski 1982, Laughlin 1983].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Early results from a phase I human trial of RS1 gene therapy showed possible closure of parafoveal schisis cavities in at least one patient.
“while early results from a phase I human trial has demonstrated potential closure of parafoveal schisis cavities in at least one patient [Bush 2016, Cukras 2018].”
Quote in the paperNot a substantial claim0 of 2 sources checked
- Premisecitation
In a canine model of RHO-associated retinitis pigmentosa, this vector preserved retinal structure and function for up to 8 months.
“This gene therapy vector has been tested in a canine model of RHO-associated retinitis pigmentosa, which showed preservation of retinal structure and function up to 8-months follow-up.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cideciyan 2018 source
Not checked in the free run.
- Premisecitation
The protein expression achieved with dual-vector therapy may be enough to slow or stop disease progression.
“In spite of this, the protein expression levels achievable may be sufficient to slow down or stop disease progression [Trapani 2015, McClements 2019].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
AAV-mediated delivery of a secreted anti-VEGF protein to the retina is a strategy for treating wet AMD.
“One strategy to alleviate the worst type of AMD (wet AMD) in which neovascularisation leads to subretinal bleeding and acute deterioration of vision is to use AAV-mediated gene therapy to express an exogenous secreted anti-vascular endothelial growth factor (anti-VEGF) protein in the retina [Constable 2016].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Constable 2016 source
Not checked in the free run.
- Premisecitation
A high vector dose needed because of the large human vitreous volume could substantially raise the risk of intraocular inflammation.
“In addition, the large volume of vitreous in humans means a high dose of vector is generally required to achieve therapeutic concentrations at the retinal surface. This could significantly increase the risk of intraocular inflammation [Bouquet 2019].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bouquet 2019 source
Not checked in the free run.
- Rests on an assumption: The large vitreous volume in humans means a high vector dose is generally needed to reach therapeutic concentrations at the retinal surface.
- Premisecitation
Packaging CRISPR gRNA and Cas9 in AAV and delivering it subretinally can specifically disrupt a disease-causing allele in photoreceptors or RPE.
“By packaging the CRISPR gRNA and Cas9 enzyme-encoding transgene within AAV and delivering the gene editing vector into the subretinal space, it is possible to specifically disrupt the disease-causing allele in the photoreceptors or RPE [Suzuki 2016; Yu 2017; McCullough 2019].”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Cideciyan et al. built an AAV vector that delivers an shRNA to silence endogenous RHO while providing a codon-modified wild-type RHO that resists RNA interference.
“Cideciyan et al. constructed an AAV vectors which delivers a short hairpin RNA (shRNA) that silences endogenous RHO gene expression while introducing a codon-modified version of wild-type RHO that is resistant to the RNA interference [Cideciyan 2018].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cideciyan 2018 source
Not checked in the free run.
- Premisecitation
A multicentre trial of Argus II in end-stage retinitis pigmentosa showed that the device supports basic visual tasks such as grating acuity, high-contrast object localisation, and motion direction detection.
“A multicentre clinical trial of Argus II in patients with end-stage retinitis pigmentosa showed that the device enables basic visual tasks, such as grating visual acuity, high contrast object localisation and detection of direction of motion.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites da Cruz 2016 source
Not checked in the free run.
- cites Schaffrath 2019 source
Not checked in the free run.
- Rests on an assumption: After outer retinal degeneration, the inner retinal circuitry from bipolar cells to retinal ganglion cells often remains intact.
- Premisecitation
Preliminary results suggest that at the optimal dose, RPGR gene replacement can reverse visual field loss in X-linked retinitis pigmentosa.
“Preliminary results have been highly encouraging, indicating that at the optimal therapeutic dose, RPGR gene replacement could lead to reversal of visual field loss in patients with X-linked retinitis pigmentosa [Cehajic-Kapetanovic 2020].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cehajic-Kapetanovic 2020 source
Not checked in the free run.
- Premisecitation
A phase I/II trial of subretinal AAV2-mediated REP1 delivery showed preserved or improved visual acuity over 2-5 years in patients with advanced choroideremia.
“A phase I/II clinical trial of subretinal gene therapy using an AAV2 vector to deliver human REP1 to the outer retina has shown sustained preservation or improvement of visual acuity over 2 to 5 years in patients with advanced disease [MacLaren 2014, Xue 2018].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisereasoning
Dual-vector gene therapy is inherently less efficient than single-vector therapy because it requires co-transduction and recombination of two fragments in the same target cell.
“Dual vector gene therapy is intrinsically less efficient compared with single vector therapy as it requires successful co-transduction and recombination of two gene fragments within the target cell.”
Quote in the paperSubstantial claim - Premisecitation
In LHON, eyes treated with gene therapy have shown little or no improvement in visual acuity.
“So far, eyes treated with gene therapy for LHON have exhibited little to no improvement in visual acuity.”
Quote in the paperNot a substantial claim0 of 2 sources checked
- May combine two claims. 10
- The quote only partly states this claim. 1
May combine two claims.
PremisecitationAAV is non-pathogenic, and multiple serotypes can efficiently and stably transduce non-dividing cells such as photoreceptors and RPE, making it an attractive retinal gene therapy vector.
“The non-pathogenic nature of AAV and the variety of viral serotypes available which can efficiently and stably transduce non-replicating cells (e.g. photoreceptors and RPE) make it a highly attractive vector for retinal gene therapy [Vandenberghe 2013].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Vandenberghe 2013 source
Not checked in the free run.
May combine two claims.
PremisecitationThe best documented grating acuity with Alpha AMS was about 0.95 logMAR (6/60 Snellen), though it varied significantly over time and between patients.
“The best documented grating visual acuity with Alpha AMS has been equivalent to around 0.95 logMAR (6/60 Snellen), although significant variations exist over time and between patients [Stingl 2017; Edwards 2018].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Stingl 2017 source
Not checked in the free run.
- cites Edwards 2018 source
Not checked in the free run.
- Rests on an assumption: After outer retinal degeneration, the inner retinal circuitry from bipolar cells to retinal ganglion cells often remains intact.
May combine two claims.
PremisecitationArgus II durability generally exceeded 5 years, and the best reported grating acuity was about 1.8 logMAR (6/379 Snellen).
“The durability of the device generally exceeded 5 years and the best reported grating visual acuity is around 1.8 logMAR equivalent (6/379 Snellen) [da Cruz 2016; Schaffrath 2019].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites da Cruz 2016 source
Not checked in the free run.
- cites Schaffrath 2019 source
Not checked in the free run.
- Rests on an assumption: After outer retinal degeneration, the inner retinal circuitry from bipolar cells to retinal ganglion cells often remains intact.
May combine two claims.
PremisecitationAAV-mediated RS1 expression in the Rs1-knockout mouse improved retinal structure, with fewer cavities, and function, as measured by electroretinogram.
“AAV-mediated augmentation of human RS1 expression in the Rs1-knockout mouse led to improved retinal structure (reduced retinal cavities) and function (electroretinogram response)”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
Premisenone givenCRISPR guide RNA directs Cas9 to a specific genomic sequence next to a PAM, creating a double-strand break; non-homologous end joining repair then produces insertions or deletions that disrupt the target gene.
“The CRISPR guide RNA (gRNA) can direct a Cas9 endonuclease to a highly specific DNA sequence within the genome adjacent to a protospacer adjacent motif (PAM) where it will create a double-strand break. Repair of the DNA break by non-homologous end joining leads to insertions or deletions that would disrupt the target gene.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationThe 22-electrode suprachoroidal device had a good safety profile and achieved Landolt-C acuity of about 2.62 logMAR (20/8397 Snellen).
“Clinical trial of the 22 electrode device achieved good safety profile and Landolt-C visual acuity equivalent of around 2.62 logMAR (20/8397 Snellen) [Ayton 2014].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ayton 2014 source
Not checked in the free run.
- Rests on an assumption: After outer retinal degeneration, the inner retinal circuitry from bipolar cells to retinal ganglion cells often remains intact.
May combine two claims.
PremisecitationPre-clinical optogenetic trials in mouse models of retinitis pigmentosa have restored basic visual function in blind animals, providing proof of principle.
“Pre-clinical trials of optogenic therapies in murine models of retinitis pigmentosa have provided proof-of-principle in restoring basic visual function to blind animals, and human clinical trials are currently underway.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Lin 2008 source
Not checked in the free run.
- cites Caporale 2011 source
Not checked in the free run.
- cites Cehajic-Kapetanovic 2015 source
Not checked in the free run.
- Rests on an assumption: After outer retinal degeneration, the inner retinal circuitry from bipolar cells to retinal ganglion cells often remains intact.
May combine two claims.
PremisecitationAfter AAV enters a mammalian cell, its DNA persists long-term in the nucleus as episomes, which are less likely than genomic integration to cause oncogenic transformation.
“Upon transduction of a target mammalian cell, the single-stranded AAV DNA undergoes second strand synthesis and subsequently persists long-term within the host nucleus in the form of monomeric or concatemeric episomes [Afione 1996, Fisher 1997]. Compared with integration into the host genome, episomes are associated with minimal risk of causing oncogenic transformation.”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationThis approach was used to transcriptionally inactivate Nrl, a master regulator of rod fate, causing rods to become cone-like cells that are relatively resistant to retinitis pigmentosa-specific mutations.
“Such a system has been used to transcriptionally inactivate the Nrl gene, a master regulator of rod fate determination. As a result, the rods became reprogrammed into cone-like cells, rendering them relatively resistant to retinitis pigmentosa-specific mutations [Moreno 2018].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Moreno 2018 source
Not checked in the free run.
The quote only partly states this claim.
InterpretationreasoningCRISPR/Cas9 gene editing is likely to be used increasingly for autosomal dominant retinal diseases.
“CRISPR/Cas9-based gene editing is likely to see increasing application in the treatment of autosomal dominant diseases.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningCharacterising the many retinal disease-causing genes is advancing understanding of retinal physiology and may enable personalised therapies for visual loss.
“Characterisation of the large number of retinal disease-causing genes is improving our understanding of retinal physiology while offering the potential for personalised therapies for visual loss.”
Quote in the paperSubstantial claim
The paper relies on this without support.
After outer retinal degeneration, the inner retinal circuitry from bipolar cells to retinal ganglion cells often remains intact.
“Once the outer retina has degenerated, it is interesting to observe that the inner retinal neural circuity from bipolar cells to retinal ganglion cells (RGCs) often remain intact.”
The paper relies on this without support.
Intravitreal AAV administration works well in rodents but is less effective in primates because the thicker inner limiting membrane restricts viral particle transit.
“Currently, intravitreal administration of AAV vectors works well in rodent models which have a small vitreous cavity and large lens, but are less effective at transducing the retina in primates due to the thicker inner limiting membrane restricting transit of viral particles.”
The paper relies on this without support.
The large vitreous volume in humans means a high vector dose is generally needed to reach therapeutic concentrations at the retinal surface.
“In addition, the large volume of vitreous in humans means a high dose of vector is generally required to achieve therapeutic concentrations at the retinal surface.”
The paper relies on this without support.
Choroideremia is an X-linked retinal dystrophy caused by loss-of-function mutations in REP1.
“Choroideremia is an X-linked retinal dystrophy caused by loss-of-function mutations in Rab escort protein 1 (REP1).”
The paper relies on this without support.
The most common X-linked retinitis pigmentosa is caused by mutations in the RPGR gene.
“For instance, the most common X-linked retinitis pigmentosa is caused by mutations within the Retinitis Pigmentosa GTPase Regulator (RPGR) gene (Fig. 2B).”
The paper relies on this without support.
About half of retinitis pigmentosa cases are autosomal dominant, and RHO mutations account for 30–40% of those.
“Approximately 50% of retinitis pigmentosa are autosomal dominant and mutations in rhodopsin (RHO), the light-sensitive G-protein-coupled receptor (GPCR) present in rods, account for 30-40% of these.”
The paper relies on this without support.
It is unclear whether AAV-mediated anti-VEGF gene therapy offers a significant clinical advantage over standard repeated intravitreal anti-VEGF injections.
“So far it is unclear whether this surgical approach offers any significant clinical advantage over the standard care of repeated intravitreal anti-VEGF antibody injections.”
The paper relies on this without support.
In patients, the exact levels of retinal cell transduction and transgene expression in vivo are unknown.
“Unlike pre-clinical testing in mouse models, one of the challenges with gene therapy in patients is that the exact levels of retinal cell transduction and transgene expression in vivo are unknown”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Prospective approaches such as gene and cell therapies or optogenetics only focus on the retina and are ineffective when pathologies irremediably damage the retina or the optic nerve.
“Prospective approaches, like gene and cell therapies or optogenetics, only focus on the retina [5,6], and they are ineffective when pathologies irremediably damage the retina or the optic nerve [7,8].”
From Advances in visual prostheses: engineering and biological challenges (2022) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Fisher citation does not match the listed author
MinorThe text cites Fisher 2017, while the corresponding 2017 reference lists Fischer as its first author.
“[Fisher 2017, Beltran 2017]”
“Fischer MD McClements ME de la Camara C Martinez-Fernandez Bellingrath JS Dauletbekov D Ramsden SC Hickey DG Barnard AR MacLaren RE Codon-Optimized RPGR Improves Stability and Efficacy of AAV8 Gene Therapy in Two Mouse Models of X-Linked Retinitis Pigmentosa Mol Ther 2017”
Man citation year does not match the reference
MinorThe text cites Man 2016, but the listed Man reference is dated 2002.
“[Man 2016]”
“Man PYW Turnbull DM Chinnery PF Leber hereditary optic neuropathy J Med Genet 2002 39 162 169”
Cites
Russell, S., Bennett, J., Wellman, J. A., Chung, D. C., Yu, Z.-F., Tillman, A., Wittes, J., Pappas, J., Elci, O., McCague, S., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31868-8 · Cited by 1,952 · see citing works
In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration
Suzuki, K., Tsunekawa, Y., Hernandez-Benitez, R., Wu, J., Zhu, J., Kim, E. J., Hatanaka, F., Yamamoto, M., Araoka, T., Li, Z., et al. (2016) · Nature · doi:10.1038/nature20565 · Cited by 1,150 · see citing works
The promise and challenge of therapeutic genome editing
Doudna, J. A. (2020) · Nature · doi:10.1038/s41586-020-1978-5 · Cited by 1,126 · cited 1× · see citing works
“…array of CRISPR genome editing molecular tools, many new therapeutic possibilities are emerging, including precise DNA base editing (to correct mutations or alter splicing), RNA editing (to correct errors within mRNA), and targeted DNA integration (to introduce large gene fragments) [Doudna 2020].”
BackgroundMaguire, A. M., High, K. A., Auricchio, A., Wright, J. F., Pierce, E. A., Testa, F., Mingozzi, F., Bennicelli, J. L., Ying, G.-S., Rossi, S., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)61836-5 · Cited by 865 · see citing works
MacLaren, R. E., Groppe, M., Barnard, A. R., Cottriall, C. L., Tolmachova, T., Seymour, L., Clark, K. R., During, M. J., Cremers, F. P. M., Black, G. C. M., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62117-0 · Cited by 796 · see citing works
Self-citationDalkara, D., Byrne, L. C., Klimczak, R. R., Visel, M., Yin, L., Merigan, W. H., Flannery, J. G., & Schaffer, D. V. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005708 · Cited by 734 · cited 1× · see citing works
“…injection, which requires high precision surgery and removal of the vitreous humor [Xue 2016], novel AAV vector serotypes are being engineered to improve their transduction efficacy, tissue tropism, and ability to penetrate the retina following simple intravitreal administration [Dalkara 2013].”
BackgroundRecombinant adeno-associated virus for muscle directed gene therapy
Fisher, K. J., Jooss, K., Alston, J., Yang, Y., Haecker, S. E., High, K., Pathak, R., Raper, S. E., & Wilson, J. M. (1997) · Nature Medicine · doi:10.1038/nm0397-306 · Cited by 654 · see citing works
Leber hereditary optic neuropathy
Man, P. Y. W., Turnbull, D. M., & Chinnery, P. F. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.3.162 · Cited by 520 · see citing works
Samulski, R. J., Berns, K. I., Tan, M., & Muzyczka, N. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.6.2077 · Cited by 466 · see citing works
Bennett, J., Wellman, J., Marshall, K. A., McCague, S., Ashtari, M., DiStefano-Pappas, J., Elci, O. U., Chung, D. C., Sun, J., Wright, J. F., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30371-3 · Cited by 461 · see citing works
Animal models of age related macular degeneration
Pennesi, M. E., Neuringer, M., & Courtney, R. J. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.06.003 · Cited by 391 · see citing works
Cehajic-Kapetanovic, J., Xue, K., Martinez-Fernandez de la Camara, C., Nanda, A., Davies, A., Wood, L. J., Salvetti, A. P., Fischer, M. D., Aylward, J. W., Barnard, A. R., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0763-1 · Cited by 368 · see citing works
Self-citationFive-year safety and performance results from the argus II retinal prosthesis system clinical trial.
da Cruz, L., Dorn, J. D., Humayun, M. S., Dagnelie, G., Handa, J., Barale, P.-O., Sahel, J.-A., Stanga, P. E., Hafezi, F., Safran, A. B., et al. (2016) · Ophthalmology · doi:10.1016/j.ophtha.2016.06.049 · Cited by 359 · see citing works
First-in-human trial of a novel suprachoroidal retinal prosthesis
Ayton, L. N., Blamey, P. J., Guymer, R. H., Luu, C. D., Nayagam, D. A. X., Sinclair, N. C., Shivdasani, M. N., Yeoh, J., McCombe, M. F., Briggs, R. J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115239 · Cited by 333 · see citing works
Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin
Lin, B., Koizumi, A., Tanaka, N., Panda, S., & Masland, R. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806114105 · Cited by 302 · see citing works
Handa, J. T., Rickman, C. B., Dick, A. D., Gorin, M. B., Miller, J. W., Toth, C. A., Ueffing, M., Zarbin, M. A., & Farrer, L. A. (2019) · Nature Communications · doi:10.1038/s41467-019-11262-1 · Cited by 280 · see citing works
Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice
Yu, W., Mookherjee, S., Chaitankar, V., Hiriyanna, S., Kim, J.-W., Brooks, M., Ataeijannati, Y., Sun, X., Dong, L., Li, T., et al. (2017) · Nature Communications · doi:10.1038/ncomms14716 · Cited by 271 · see citing works
Cukras, C., Wiley, H. E., Jeffrey, B. G., Sen, H. N., Turriff, A., Zeng, Y., Vijayasarathy, C., Marangoni, D., Ziccardi, L., Kjellstrom, S., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.05.025 · Cited by 268 · cited 1× · see citing works
“…in the Rs1-knockout mouse led to improved retinal structure (reduced retinal cavities) and function (electroretinogram response), while early results from a phase I human trial has demonstrated potential closure of parafoveal schisis cavities in at least one patient [Bush 2016, Cukras 2018].”
BackgroundCloning of infectious adeno-associated virus genomes in bacterial plasmids
Laughlin, C. A., Tratschin, J.-D., Coon, H., & Carter, B. J. (1983) · Gene · doi:10.1016/0378-1119(83)90217-2 · Cited by 266 · see citing works
In vivo model of adeno-associated virus vector persistence and rescue
Afione, S. A., Conrad, C. K., Kearns, W. G., Chunduru, S., Adams, R., Reynolds, T. C., Guggino, W. B., Cutting, G. R., Carter, B. J., & Flotte, T. R. (1996) · Journal of Virology · doi:10.1128/jvi.70.5.3235-3241.1996 · Cited by 223 · see citing works
Gene Therapy for Leber Hereditary Optic Neuropathy
Guy, J., Feuer, W. J., Davis, J. L., Porciatti, V., Gonzalez, P. J., Koilkonda, R. D., Yuan, H., Hauswirth, W. W., & Lam, B. L. (2017) · Ophthalmology · doi:10.1016/j.ophtha.2017.05.016 · Cited by 204 · see citing works
Stingl, K., Schippert, R., Bartz-Schmidt, K. U., Besch, D., Cottriall, C. L., Edwards, T. L., Gekeler, F., Greppmaier, U., Kiel, K., Koitschev, A., et al. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00445 · Cited by 198 · see citing works
Self-citationVisual Acuity after Retinal Gene Therapy for Choroideremia
Edwards, T. L., Jolly, J. K., Groppe, M., Barnard, A. R., Cottriall, C. L., Tolmachova, T., Black, G. C., Webster, A. R., Lotery, A. J., Holder, G. E., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmc1509501 · Cited by 195 · see citing works
Self-citationEdwards, T. L., Cottriall, C. L., Xue, K., Simunovic, M. P., Ramsden, J. D., Zrenner, E., & MacLaren, R. E. (2018) · Ophthalmology · doi:10.1016/j.ophtha.2017.09.019 · Cited by 193 · see citing works
Self-citationTechnique of retinal gene therapy: delivery of viral vector into the subretinal space
Xue, K., Groppe, M., Salvetti, A. P., & MacLaren, R. E. (2017) · Eye · doi:10.1038/eye.2017.158 · Cited by 191 · see citing works
Self-citationBeneficial effects on vision in patients undergoing retinal gene therapy for choroideremia
Xue, K., Jolly, J. K., Barnard, A. R., Rudenko, A., Salvetti, A. P., Patrício, M. I., Edwards, T. L., Groppe, M., Orlans, H. O., Tolmachova, T., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0185-5 · Cited by 185 · see citing works
Self-citationRestoration of vision with ectopic expression of human rod opsin
Cehajic-Kapetanovic, J., Eleftheriou, C., Allen, A. E., Milosavljevic, N., Pienaar, A., Bedford, R., Davis, K. E., Bishop, P. N., & Lucas, R. J. (2015) · Current Biology · doi:10.1016/j.cub.2015.07.029 · Cited by 184 · see citing works
LiGluR restores visual responses in rodent models of inherited blindness
Caporale, N., Kolstad, K. D., Lee, T., Tochitsky, I., Dalkara, D., Trauner, D., Kramer, R., Dan, Y., Isacoff, E. Y., & Flannery, J. G. (2011) · Molecular Therapy · doi:10.1038/mt.2011.103 · Cited by 182 · see citing works
In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation
Moreno, A. M., Fu, X., Zhu, J., Katrekar, D., Shih, Y.-R. V., Marlett, J., Cabotaje, J., Tat, J., Naughton, J., Lisowski, L., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.04.017 · Cited by 159 · see citing works
The promise and challenge of therapeutic genome editing
Doudna, & Já (2020) · 四川生理科学杂志 · Cited by 153 · see citing works
Constable, I. J., Pierce, C. M., Lai, C.-M., Magno, A. L., Degli-Esposti, M. A., French, M. A., McAllister, I. L., Butler, S., Barone, S. B., Schwartz, S. D., et al. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.11.016 · Cited by 152 · see citing works
Restoration of high-sensitivity and adapting vision with a cone opsin
Berry, M. H., Holt, A., Salari, A., Veit, J., Visel, M., Levitz, J., Aghi, K., Gaub, B. M., Sivyer, B., Flannery, J. G., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09124-x · Cited by 152 · see citing works
Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector
Cideciyan, A. V., Sudharsan, R., Dufour, V. L., Massengill, M. T., Iwabe, S., Swider, M., Lisi, B., Sumaroka, A., Marinho, L. F., Appelbaum, T., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1805055115 · Cited by 147 · see citing works
Fischer, M. D., McClements, M. E., Martinez-Fernandez de la Camara, C., Bellingrath, J.-S., Dauletbekov, D., Ramsden, S. C., Hickey, D. G., Barnard, A. R., & MacLaren, R. E. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.05.005 · Cited by 112 · see citing works
Self-citationBouquet, C., Vignal Clermont, C., Galy, A., Fitoussi, S., Blouin, L., Munk, M. R., Valero, S., Meunier, S., Katz, B., Sahel, J. A., et al. (2019) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2018.6902 · Cited by 102 · cited 2× · see citing works
“Both approaches are currently being tested in clinical trials [Guy 2017, Bouquet 2019].”
BackgroundMethodAAV9 targets cone photoreceptors in the nonhuman primate retina
Vandenberghe, L. H., Bell, P., Maguire, A. M., Xiao, R., Hopkins, T. B., Grant, R., Bennett, J., & Wilson, J. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053463 · Cited by 97 · see citing works
Trapani, I., Toriello, E., de Simone, S., Colella, P., Iodice, C., Polishchuk, E. V., Sommella, A., Colecchi, L., Rossi, S., Simonelli, F., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv386 · Cited by 94 · see citing works
McClements, M. E., Barnard, A. R., Singh, M. S., Charbel Issa, P., Jiang, Z., Radu, R. A., & MacLaren, R. E. (2019) · Human Gene Therapy · doi:10.1089/hum.2018.156 · Cited by 92 · see citing works
Self-citationSilva, S. R. D., Barnard, A. R., Hughes, S., Tam, S. K. E., Martin, C. J., Singh, M. S., Barnea-Cramer, A. O., McClements, M. E., During, M. J., Peirson, S. N., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701589114 · Cited by 89 · see citing works
Self-citationBush, R. A., Zeng, Y., Colosi, P., Kjellstrom, S., Hiriyanna, S., Vijayasarathy, C., Santos, M., Li, J., Wu, Z., & Sieving, P. A. (2016) · Human Gene Therapy · doi:10.1089/hum.2015.142 · Cited by 86 · see citing works
Optimization of Retinal Gene Therapy for X-Linked Retinitis Pigmentosa Due to RPGR Mutations
Beltran, W. A., Cideciyan, A. V., Boye, S. E., Ye, G.-J., Iwabe, S., Dufour, V. L., Marinho, L. F., Swider, M., Kosyk, M. S., Sha, J., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.05.004 · Cited by 82 · see citing works
McCullough, K. T., Boye, S. L., Fajardo, D., Calabro, K., Peterson, J. J., Strang, C. E., Chakraborty, D., Gloskowski, S., Haskett, S., Samuelsson, S., et al. (2019) · Human Gene Therapy · doi:10.1089/hum.2018.193 · Cited by 79 · see citing works
Zarbin, M. A., Sugino, I. K., & Townes‐Anderson, E. (2019) · Stem Cells Translational Medicine · doi:10.1002/sctm.18-0282 · Cited by 74 · see citing works
One-Year Safety and Performance Assessment of the Argus II Retinal Prosthesis: A Postapproval Study
Schaffrath, K., Schellhase, H., Walter, P., Augustin, A., Chizzolini, M., Kirchhof, B., Grisanti, S., Wiedemann, P., Szurman, P., Richard, G., et al. (2019) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2019.1476 · Cited by 44 · see citing works
Correction: AAV9 Targets Cone Photoreceptors in the Nonhuman Primate Retina
Vandenberghe, L. H., Bell, P., Maguire, A. M., Xiao, R., Hopkins, T. B., Grant, R., Bennett, J., & Wilson, J. M. (2013) · PLoS ONE · doi:10.1371/annotation/64b90996-4634-4c63-b737-634397b0b445 · Cited by 16 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Man, 2002, J Med Genet
Cited by
Sorted by citations
Advances in visual prostheses: engineering and biological challenges
Borda, E., & Ghezzi, D. (2022) · Progress in Biomedical Engineering · doi:10.1088/2516-1091/ac812c · Cited by 44 · see citing works
Clinical Progress and Optimization of Information Processing in Artificial Visual Prostheses
Wang, J., Zhao, R., Li, P., Fang, Z., Li, Q., Han, Y., Zhou, R., & Zhang, Y. (2022) · Sensors · doi:10.3390/s22176544 · Cited by 10 · see citing works
CRISPR Cas9 based genome editing in inherited retinal dystrophies
Bansal, M., Acharya, S., Sharma, S., Phutela, R., Rauthan, R., Maiti, S., & Chakraborty, D. (2021) · Ophthalmic Genetics · doi:10.1080/13816810.2021.1904421 · Cited by 10 · see citing works
Stemerdink, M., Malinar, L., Broekman, S., Peters, T. A., Ensink, I., Ivanchenko, M. V., Venselaar, H., Kremer, H., de Vrieze, E., & van Wijk, E. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102702 · Cited by 1 · see citing works
Differential temporal filtering in the fly optic lobe
Borst, A. (2025) · Journal of Computational Neuroscience · doi:10.1007/s10827-025-00914-5
- Authors
- Xue, K., & MacLaren, R. E.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Xue, Kanmin
- Venue
- Current Opinion in Physiology
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 16
- Pages
- 1-7
- ISSN
- 2468-8673 (ISSN-L)
- PMC
- PMC7115840
- OpenAlex
- W3020304635
- Semantic Scholar
- ff22cf87789e91ce6c10e570beb0516ebb64f8b1
- Cited by
- 5
- References
- 45
- Citations by year
- 2025: 2 · 2022: 2 · 2021: 1
- FWCI
- 0.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Physiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Keywords
- retinal degeneration, blindness, gene therapy, genome editing, CRISPR/Cas9, optogenetics, retinal prosthesis, gene delivery vectors, clinical trials
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
