Induction of rapid and highly efficient expression of the human ND4 complex I subunit in the mouse visual system by self-complementary adeno-associated virus
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OBJECTIVE: To demonstrate the high efficiency and rapidity of allotopic expression of a normal human ND4 subunit of complex I in the vertebrate retina using a self-complementary adeno-associated virus (scAAV) vector for ocular gene delivery to treat acute visual loss in Leber hereditary optic neuropathy (LHON). METHODS: The nuclear-encoded human ND4 subunit fused to the P1 isoform of subunit C of adenosine triphosphate synthase (ATPc) mitochondrial targeting sequence and FLAG epitope was packaged in scAAV2 capsids or single-stranded (ss) AAV2 capsids. These constructs were injected into the vitreous cavities of mice. The contralateral eyes were injected with scAAV-green fluorescent protein (GFP). One week later, pattern electroretinograms and gene expression of the human ND4 subunit and GFP were evaluated. Quantitative analysis of ND4FLAG-injected eyes was assessed relative to Thy1.2-labeled retinal ganglion cells (RGCs). RESULTS: Pattern electroretinogram amplitudes remained normal in eyes inoculated with scAAV-ND4FLAG, ssAAV-ND4FLAG, and GFP. Confocal microscopy revealed the typical perinuclear mitochondrial expression of scAAV-ND4FLAG in almost the entire retinal flat mount. In contrast, scAAV-GFP expression was cytoplasmic and nuclear. Relative to Thy1.2-positive RGCs, quantification of scAAV-ND4FLAG-positive RGCs was 91% and that of ssAAV-ND4FLAG-positive RGCs was 51%. CONCLUSION: Treatment of acute visual loss due to LHON may be possible with a normal human ND4 subunit gene of complex I, mutated in most cases of LHON, when delivered by an scAAV vector. Clinical Relevance Unlike most retinal degenerations that result in slowly progressive loss of vision over many years, LHON due to mutated mitochondrial DNA results in apoplectic, bilateral severe and usually irreversible visual loss. For rescue of acute visual loss in LHON, a highly efficient and rapid gene expression system is required.
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Preclinical studies showed that rAAV2/2-ND4 efficiently rescued complex I dysfunction in cells carrying the m.11778G>A mutation and in an induced rat model of LHON.
“Preclinical studies showed that rAAV2/2-ND4 efficiently rescued complex I dysfunction in cells carrying the m.11778G>A mutation and in an induced rat model of LHON.[12][13][14][15]”
From Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset (2021) · cites this paper as [14]
The Clinical Relevance section (page not provided) reports that normal ND4 expression normalized defective ATP synthesis in LHON cells, but does not establish that rAAV2/2-ND4 produced that rescue. The Comment section (page not provided) reports prevention of visual loss in an induced rat model, but specifies that the ND4 gene was delivered by plasmid electroporation, not AAV. This paper's own mouse results concern efficient ND4 expression rather than rescue of complex I dysfunction. (LLM, conf=0.87)
Experimental — accuracy not yet measuredWhen compared to ssDNA, lowered rAAV doses of scAAV gene therapy vector can be used to reach similar transgene expression levels in the retina in vivo.
“When compared to ssDNA, lowered rAAV doses of scAAV gene therapy vector can be used to reach similar transgene expression levels in the retina in vivo [101,152,256,257].”
From Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays (2020) · cites this paper as [256]
The Methods (Intraocular Injections) report a lower dose of scAAV than ssAAV in mice. The Results (Immunohistochemistry) report ND4 expression in 91% of retinal ganglion cells with scAAV versus 51% with ssAAV. This supports greater expression at a lower dose, but the paper does not show that a reduced scAAV dose reaches a similar expression level to ssAAV. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe allotopic expression strategy has been successfully applied in cell models and safely translated in induced rodent LHON models with preservation of RGCs and visual function.
“This strategy has been successfully applied in cell models and safely translated in induced rodent LHON models with preservation of RGCs and visual function.9–12”
From Randomized trial of bilateral gene therapy injection for m.11778G&gt;A <i>MT-ND4</i> Leber optic neuropathy (2023) · cites this paper as [10]
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Cites
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 · see citing works
Gene therapy restores vision in a canine model of childhood blindness
Acland, G. M., Aguirre, G. D., Ray, J., Zhang, Q., Aleman, T. S., Cideciyan, A. V., Pearce-Kelling, S. E., Anand, V., Zeng, Y., Maguire, A. M., et al. (2001) · Nature Genetics · doi:10.1038/ng0501-92 · Cited by 1,202 · see citing works
PROTEIN IMPORT INTO MITOCHONDRIA
Neupert, W. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.863 · Cited by 1,060 · see citing works
[Protein import into mitochondria].
Zaĭtseva, L. G., Tv, O., & Grinkevich, V. A. (2000) · PubMed · Cited by 971 · see citing works
Hauswirth, W. W., Aleman, T. S., Kaushal, S., Cideciyan, A. V., Schwartz, S. B., Wang, L., Conlon, T. J., Boye, S. L., Flotte, T. R., Byrne, B. J., et al. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.107 · Cited by 954 · see citing works
Rabinowitz, J. E., Rolling, F., Li, C., Conrath, H., Xiao, W., Xiao, X., & Samulski, R. J. (2002) · Journal of Virology · doi:10.1128/jvi.76.2.791-801.2002 · Cited by 762 · see citing works
Keeney, P., Xie, J., Capaldi, R., & Bennett, J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0984-06.2006 · Cited by 757 · see citing works
McCarty, D., Monahan, P., & Samulski, R. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301514 · Cited by 735 · see citing works
The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy
Xie, Q., Bu, W., Bhatia, S., Hare, J., Somasundaram, T., Azzi, A., & Chapman, M. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162250899 · Cited by 612 · see citing works
IMPORT OF PROTEINS INTO MITOCHONDRIA
Glick, B. S., & Schatz, G. (1991) · Annual Review of Genetics · doi:10.1146/annurev.ge.25.120191.000321 · Cited by 579 · see citing works
Mitochondrial gene replacement in primate offspring and embryonic stem cells
Tachibana, M., Sparman, M. L., Sritanaudomchai, H., Ma, H., Clepper, L., Woodward, J., Li, Y., Ramsey, C. M., Kolotushkina, O., & Mitalipov, S. M. (2009) · Nature · doi:10.1038/nature08368 · Cited by 565 · see citing works
Zhong, L., Li, B., Mah, C. S., Govindasamy, L., Agbandje-McKenna, M., Cooper, M., Herzog, R. W., Zolotukhin, I., Warrington, K. H., Weigel-Van Aken, K. A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802866105 · Cited by 558 · see citing works
McCarty, D. M., Fu, H., Monahan, P. E., Toulson, C. E., Naik, P., & Samulski, R. J. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302134 · Cited by 547 · see citing works
Riordan‐Eva, P., Sanders, M. D., Govan, G. G., Sweeney, M. G., Costa, J. D., & Harding, A. E. (1995) · Brain · doi:10.1093/brain/118.2.319 · Cited by 490 · see citing works
Nathwani, A. C., Gray, J. T., Ng, C. Y., Zhou, J., Spence, Y., Waddington, S. N., Tuddenham, E. G. D., Kemball‐Cook, G., McIntosh, J., Boon‐Spijker, M., et al. (2005) · Blood · doi:10.1182/blood-2005-10-4035 · Cited by 421 · see citing works
High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors
Petrs-Silva, H., Dinculescu, A., Li, Q., Min, S.-H., Chiodo, V., Pang, J.-J., Zhong, L., Zolotukhin, S., Srivastava, A., Lewin, A. S., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2008.269 · Cited by 398 · see citing works
Manfredi, G., Fu, J., Ojaimi, J., Sadlock, J., Kwong, J. Q., Guy, J., & Schon, E. (2002) · Nature Genetics · doi:10.1038/ng851 · Cited by 282 · see citing works
Rescue of a mitochondrial deficiency causing Leber hereditary optic neuropathy
Guy, J. R., Qi, X., Pallotti, F., Schon, E. A., Manfredi, G., Carelli, V., Martinuzzi, A., Hauswirth, W. W., & Lewin, A. S. (2002) · Annals of Neurology · doi:10.1002/ana.10354 · Cited by 273 · see citing works
Adeno-associated virus: from defective virus to effective vector
Gonçalves, M. A. F. V. (2005) · Virology Journal · doi:10.1186/1743-422x-2-43 · Cited by 266 · see citing works
Luján-Huertas, S. (2005) · Angiología · doi:10.1016/s0003-3170(05)74921-x · Cited by 225 · see citing works
Peden, C. S., Burger, C., Muzyczka, N., & Mandel, R. J. (2004) · Journal of Virology · doi:10.1128/jvi.78.12.6344-6359.2004 · Cited by 222 · see citing works
Ellouze, S., Augustin, S., Bouaita, A., Bonnet, C., Simonutti, M., Forster, V., Picaud, S. A., Sahel, J., & Corral‐Debrinski, M. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.08.013 · Cited by 222 · see citing works
Protein Import Into Mitochondria
Paschen, S. A., & Neupert, W. (2001) · IUBMB Life · doi:10.1080/15216540152845894 · Cited by 222 · see citing works
(2008) · PubMed Central · Cited by 183 · see citing works
Fu, H., Muenzer, J., Samulski, R. J., Breese, G. R., Sifford, J., Zeng, X., & McCarty, D. M. (2003) · Molecular Therapy · doi:10.1016/j.ymthe.2003.08.021 · Cited by 181 · see citing works
Immunity to adeno-associated virus vectors in animals and humans: a continued challenge
Zaiss, A. K., & Muruve, D. A. (2008) · Gene Therapy · doi:10.1038/gt.2008.54 · Cited by 179 · see citing works
Bayona‐Bafaluy, M. P., Blits, B., Battersby, B. J., Shoubridge, E. A., & Moraes, C. T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502896102 · Cited by 169 · see citing works
Persistent transgene product in retina, optic nerve and brain after intraocular injection of rAAV
Dudus, L., Anand, V., Acland, G. M., Chen, S.-J., Wilson, J. M., Fisher, K. J., Maguire, A. M., & Bennett, J. (1999) · Vision Research · doi:10.1016/s0042-6989(98)00308-3 · Cited by 160 · see citing works
Approaches to the treatment of mitochondrial diseases
DiMauro, S., Hirano, M., & Schon, E. A. (2006) · Muscle & Nerve · doi:10.1002/mus.20598 · Cited by 138 · see citing works
The Mutant Human ND4 Subunit of Complex I Induces Optic Neuropathy in the Mouse
Qi, X., Sun, L., Lewin, A. S., Hauswirth, W. W., & Guy, J. R. (2006) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0789 · Cited by 118 · see citing works
Guy, J. (1999) · Archives of Ophthalmology · doi:10.1001/archopht.117.7.929 · Cited by 114 · see citing works
Limitations of Allotopic Expression of Mitochondrial Genes in Mammalian Cells
Oca‐Cossio, J., Kenyon, L., Hao, H., & Moraes, C. T. (2003) · Genetics · doi:10.1093/genetics/165.2.707 · Cited by 107 · see citing works
Newman, N. J., Biousse, V., David, R., Bhatti, M. T., Hamilton, S. R., Farris, B. K., Lesser, R. L., Newman, S. A., Turbin, R. E., Chen, K., et al. (2005) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2005.03.058 · Cited by 105 · see citing works
IOP-Dependent Retinal Ganglion Cell Dysfunction in Glaucomatous DBA/2J Mice
Nagaraju, M., Saleh, M., & Porciatti, V. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0582 · Cited by 103 · see citing works
Bacman, S. R., Williams, S. L., Hernandez, D., & Moraes, C. T. (2007) · Gene Therapy · doi:10.1038/sj.gt.3302981 · Cited by 93 · see citing works
Mitochondrial Gene Therapy Augments Mitochondrial Physiology in a Parkinson's Disease Cell Model
Keeney, P. M., Quigley, C. K., Dunham, L. D., Papageorge, C. M., Iyer, S., Thomas, R. R., Schwarz, K. M., Trimmer, P. A., Khan, S. M., Portell, F. R., et al. (2009) · Human Gene Therapy · doi:10.1089/hum.2009.023 · Cited by 88 · see citing works
Guy, J. R., Qi, X., Koilkonda, R. D., Arguello, T., Chou, T.-H., Ruggeri, M., Porciatti, V., Lewin, A. S., & Hauswirth, W. W. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-3214 · Cited by 84 · see citing works
Self-citationIn Vivo Complementation of Complex I by the Yeast Ndi1 Enzyme
Seo, B. B., Nakamaru‐Ogiso, E., Flotte, T. R., Matsuno‐Yagi, A., & Yagi, T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600922200 · Cited by 83 · see citing works
Custom Adeno-Associated Virus Capsids: The Next Generation of Recombinant Vectors with Novel Tropism
Muzyczka, N., & Warrington, K. H. (2005) · Human Gene Therapy · doi:10.1089/hum.2005.16.408 · Cited by 80 · see citing works
Gao, G., Lü, Y., Sun, X., Johnston, J., Calcedo, R., Grant, R. L., & Wilson, J. M. (2006) · Journal of Virology · doi:10.1128/jvi.00526-06 · Cited by 78 · see citing works
Ocular gene transfer with self-complementary AAV vectors
Yokoi, K., Kachi, S., Zhang, H. S., Gregory, P. D., Spratt, S. K., Samulski, R. J., & Campochiaro, P. A. (2007) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.06-1306 · Cited by 58 · see citing works
Mechanisms of AAV transduction in glaucoma‐associated human trabecular meshwork cells
Borrás, T., Xue, W., Choi, V. W., Bartlett, J. S., Li, G., Samulski, R. J., & Chisolm, S. S. (2006) · The Journal of Gene Medicine · doi:10.1002/jgm.886 · Cited by 52 · see citing works
Andino, L. M., Conlon, T. J., Porvasnik, S., Boye, S. L., Hauswirth, W. W., & Lewin, A. S. (2007) · Genetic Vaccines and Therapy · doi:10.1186/1479-0556-5-13 · Cited by 17 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [2]Harding AE Sweeney MG Govan GG Riordan-Eva P Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation. Am J Hum Genet 1995 57 1 77 86 7611298 PMC1801226
- [23]Hauswirth WW Lewin AS Zolotukhin S Muzyczka N Palczewski K Production and purification of recombinant AAV vectors. Vertebrate Phototransduction and the Visual Cycle 2000 743 761 Academic Press Inc Orlando, FL
Cited by
Sorted by citations
Yu-Wai-Man, P., Newman, N. J., Carelli, V., Moster, M. L., Biousse, V., Sadun, A. A., Klopstock, T., Vignal-Clermont, C., Sergott, R. C., Rudolph, G., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz7423 · Cited by 232 · see citing works
Gene Therapy for Leber Hereditary Optic Neuropathy
Feuer, W. J., Schiffman, J. C., Davis, J. L., Porciatti, V., Gonzalez, P., Koilkonda, R. D., Yuan, H., Lalwani, A., Lam, B. L., & Guy, J. (2016) · Ophthalmology · doi:10.1016/j.ophtha.2015.10.025 · Cited by 230 · see citing works
Self-citationGene 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
Self-citationPunzo, C., Xiong, W., & Cepko, C. L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.304428 · Cited by 181 · see citing works
Newman, N. J., Yu-Wai-Man, P., Carelli, V., Moster, M. L., Biousse, V., Vignal-Clermont, C., Sergott, R. C., Klopstock, T., Sadun, A. A., Barboni, P., et al. (2021) · Ophthalmology · doi:10.1016/j.ophtha.2020.12.012 · Cited by 168 · see citing works
Koilkonda, R. D., Yu, H., Chou, T.-H., Feuer, W. J., Ruggeri, M., Porciatti, V., Tse, D., Hauswirth, W. W., Chiodo, V. A., Boye, S. L., et al. (2014) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2013.7630 · Cited by 102 · see citing works
Self-citationBuck, T., & Wijnholds, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124197 · Cited by 92 · see citing works
“When compared to ssDNA, lowered rAAV doses of scAAV gene therapy vector can be used to reach similar transgene expression levels in the retina in vivo [101,152,256,257].”
BackgroundLam, B. L., Feuer, W. J., Schiffman, J. C., Porciatti, V., Vandenbroucke, R., Rosa, P. R., Gregori, G., & Guy, J. (2014) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2013.7971 · Cited by 96 · see citing works
Therapeutic Options in Hereditary Optic Neuropathies
Amore, G., Romagnoli, M., Carbonelli, M., Barboni, P., Carelli, V., & Morgia, C. L. (2020) · Drugs · doi:10.1007/s40265-020-01428-3 · Cited by 95 · see citing works
Newman, N. J., Yu-Wai-Man, P., Subramanian, P. S., Moster, M. L., Wang, A.-G., Donahue, S. P., Leroy, B. P., Carelli, V., Biousse, V., Vignal-Clermont, C., et al. (2023) · Brain · doi:10.1093/brain/awac421 · Cited by 87 · see citing works
Advances in AAV Vector Development for Gene Therapy in the Retina
Day, T. P., Byrne, L. C., Schaffer, D. V., & Flannery, J. G. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3209-8_86 · Cited by 71 · see citing works
Leber's Hereditary Optic Neuropathy-Gene Therapy: From Benchtop to Bedside
Koilkonda, R. D., & Guy, J. R. (2010) · Journal of Ophthalmology · doi:10.1155/2011/179412 · Cited by 66 · see citing works
Self-citationKoilkonda, R., Yu, H., Talla, V., Porciatti, V., Feuer, W. J., Hauswirth, W. W., Chiodo, V., Erger, K. E., Boye, S. L., Lewin, A. S., et al. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-15388 · Cited by 65 · see citing works
Self-citationLeber Hereditary Optic Neuropathy: Exemplar of an mtDNA Disease
Wallace, D. C., & Lott, M. T. (2017) · Handbook of experimental pharmacology · doi:10.1007/164_2017_2 · Cited by 64 · see citing works
Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant
Boominathan, A., Vanhoozer, S., Basisty, N., Powers, K., Crampton, A. L., Wang, X., Friedricks, N., Schilling, B., Brand, M. D., & O’Connor, M. S. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw756 · Cited by 52 · see citing works
Ratican, S., Osborne, A., & Martin, K. R. G. (2018) · Neural Plasticity · doi:10.1155/2018/7108948 · Cited by 44 · see citing works
Biodistribution of intravitreal lenadogene nolparvovec gene therapy in nonhuman primates
Calkins, D. J., Yu-Wai-Man, P., Newman, N. J., Taiel, M., Singh, P., Chalmey, C., Rogue, A., Carelli, V., Ancian, P., & Sahel, J. A. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.09.013 · Cited by 37 · see citing works
Liu, H., Yuan, J., Zhang, Y., Tian, Z., Li, X., Wang, D., Du, Y., Song, L., & Li, B. (2020) · Acta Ophthalmologica · doi:10.1111/aos.14379 · Cited by 35 · see citing works
A novel retinal ganglion cell promoter for utility in AAV vectors
Hanlon, K. S., Chadderton, N., Palfi, A., Blanco Fernandez, A., Humphries, P., Kenna, P. F., Millington-Ward, S., & Farrar, G. J. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00521 · Cited by 34 · see citing works
Emerging Gene Therapies for Retinal Degenerations
Cepko, C. L. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0295-12.2012 · Cited by 31 · see citing works
C57BL/6J, DBA/2J, and DBA/2J.Gpnmb mice have different visual signal processing in the inner retina.
Porciatti, V., Chou, T.-H., & Feuer, W. J. (2010) · Europe PMC (PubMed Central) · Cited by 32 · see citing works
Voretigene Neparvovec and Gene Therapy for Leber’s Congenital Amaurosis: Review of Evidence to Date
Padhy, S. K., Takkar, B., Narayanan, R., Venkatesh, P., & Jalali, S. (2020) · The Application of Clinical Genetics · doi:10.2147/tacg.s230720 · Cited by 31 · see citing works
Post-Vitrectomy Endophthalmitis in Victoria, Australia
Chandra, A., Smith, J. D., Wang, B. Z., Kurniawan, E. D., Kam, J., Sandhu, S. S., & Allen, P. J. (2016) · Asia-Pacific Journal of Ophthalmology · doi:10.22608/apo.2016126 · Cited by 28 · see citing works
Raj, D., Davidoff, A. M., & Nathwani, A. C. (2011) · Expert Review of Hematology · doi:10.1586/ehm.11.48 · Cited by 27 · see citing works
Current and Future Landscape in Genetic Therapies for Leber Hereditary Optic Neuropathy
Shamsnajafabadi, H., MacLaren, R. E., & Cehajic‐Kapetanovic, J. (2023) · Cells · doi:10.3390/cells12152013 · Cited by 25 · see citing works
The Progress of Gene Therapy for Leber's Optic Hereditary Neuropathy
Zhang, Y., Tian, Z., Yuan, J., Liu, C. X., Liu, H. L., Qi, S., & Li, B. (2018) · Current Gene Therapy · doi:10.2174/1566523218666171129204926 · Cited by 25 · see citing works
Talla, V., Yang, C., Shaw, G., Porciatti, V., Koilkonda, R. D., & Guy, J. R. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-11899 · Cited by 19 · see citing works
Self-citationDevi, S. M., Abishek Kumar, B., Iyer, M., & Vellingiri, B. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.08.013 · Cited by 18 · see citing works
Dawn of ocular gene therapy: implications for molecular diagnosis in retinal disease
Zaneveld, J. E., Wang, F., Wang, X., & Chen, R. (2013) · Science China Life Sciences · doi:10.1007/s11427-013-4443-y · Cited by 17 · see citing works
Adeno‐associated virus‐mediated gene delivery of the human ND4 complex I subunit in rabbit eyes
Shi, H. R., Gao, J., Pei, H., Liu, R., Hu, W., Wan, X., Li, T., & Li, B. (2012) · Clinical and Experimental Ophthalmology · doi:10.1111/j.1442-9071.2012.02815.x · Cited by 16 · see citing works
Gene-agnostic approaches to treating inherited retinal degenerations
Chew, L. A., & Iannaccone, A. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1177838 · Cited by 16 · see citing works
Optic Neurodegeneration: Time to Act
Gueven, N. (2014) · Biology and Medicine · doi:10.4172/0974-8369.s1-001 · Cited by 13 · see citing works
Gene therapies for inherited retinal disorders
Farrar, G. J., Millington‐Ward, S., Chadderton, N., Mansergh, F. C., & Palfi, A. (2014) · Visual Neuroscience · doi:10.1017/s0952523814000133 · Cited by 12 · see citing works
The Mitochondrial Genome in Aging and Disease and the Future of Mitochondrial Therapeutics
Saravanan, S., Lewis, C. J., Dixit, B., O’Connor, M. S., Stolzing, A., & Boominathan, A. (2022) · Biomedicines · doi:10.3390/biomedicines10020490 · Cited by 13 · see citing works
Gene therapy for the mitochondrial genome: Purging mutations, pacifying ailments
Siva, A., Mahalakshmi, R., Bhakta-Guha, D., & Guha, G. (2018) · Mitochondrion · doi:10.1016/j.mito.2018.06.002 · Cited by 12 · see citing works
The constraints of allotopic expression
Nieto-Panqueva, F., Rubalcava-Gracia, D., Hamel, P. P., & González‐Halphen, D. (2023) · Mitochondrion · doi:10.1016/j.mito.2023.09.004 · Cited by 9 · see citing works
Advantages and disadvantages of molecular testing in ophthalmology
Sutherland, J. E., & Day, M. A. (2011) · Expert Review of Ophthalmology · doi:10.1586/eop.11.2 · Cited by 8 · see citing works
Leber Hereditary Optic Neuropathy: Molecular Pathophysiology and Updates on Gene Therapy
Chi, S.-C., Cheng, H., & Wang, A.-G. (2022) · Biomedicines · doi:10.3390/biomedicines10081930 · Cited by 7 · see citing works
Mitochondrial Biology and Medicine
Wallace, D. C., Lott, M. T., & Procaccio, V. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-812537-3.00010-x · Cited by 7 · see citing works
Wallace, D. C., Lott, M. T., & Procaccio, V. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-383834-6.00013-6 · Cited by 7 · see citing works
Newman, N. J., Schniederjan, M., Mendoza, P. R., Calkins, D. J., Yu‐Wai‐Man, P., Biousse, V., Carelli, V., Taiel, M., Rugiero, F., Singh, P., et al. (2022) · BMC Neurology · doi:10.1186/s12883-022-02787-y · Cited by 6 · see citing works
Thampi, P., Seabaugh, K. A., Pezzanite, L. M., Chu, C. R., Phillips, J. N., Grieger, J. C., McIlwraith, C. W., Samulski, R. J., & Goodrich, L. R. (2023) · Gene Therapy · doi:10.1038/s41434-023-00420-2 · Cited by 5 · see citing works
Advanced therapies for inherited optic neuropathies
Wong, D., Makam, R., & Yu‐Wai‐Man, P. (2025) · Eye · doi:10.1038/s41433-025-04109-1 · Cited by 5 · see citing works
AAV-Mediated Gene Therapy for CRB1-Hereditary Retinopathies
Alves, C. H., & Wijnholds, J. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.79308 · Cited by 3 · see citing works
Retinal Degenerations: Genetics, Mechanisms, and Therapies
MacDonald, I. M., Naash, M. I., & Ayyagari, R. (2011) · Journal of Ophthalmology · doi:10.1155/2011/764873 · Cited by 1 · see citing works
mice have different visual signal processing in the inner retina
Porciatti, V., Chou, T., & Feuer, W. J. (2010)
An Early Case of Leber’s Hereditary Optic Neuropathy to Diagnose and Treat
王, 丹. (2017) · Hans Journal of Ophthalmology · doi:10.12677/hjo.2017.62008
Adeno-Associated Virus (AAV)-Mediated Gene Therapy for Leber Hereditary Optic Neuropathy
Xie, K., Ming, S., Yang, M., Jin, X., & Lei, B. (2018) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-981-13-0884-0_22
- Authors
- Koilkonda, R. D.
- Affiliations
- University of Miami (US)
- Corresponding author
- Koilkonda, Rajeshwari D.
- Venue
- Archives of Ophthalmology
- Publisher
- American Medical Association (AMA)
- Published
- 2010-07-01
- Volume
- 128
- Issue
- 7
- Pages
- 876
- ISSN
- 0003-9950 (ISSN-L)
- PMC
- PMC3431796
- OpenAlex
- W2060065962
- Cited by
- 48
- References
- 42
- Citations by year
- 2025: 1 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 1 · 2014: 6 · 2013: 3 · 2012: 2
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (P30-EY14801, R24EY018600, R01EY017141, P30EY014801)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- Leber's hereditary optic neuropathy, ocular gene delivery, mitochondrial DNA mutations, retinal ganglion cells, pattern electroretinogram, mitochondrial targeting sequence, intravitreal injection, acute visual loss, retinal degeneration
- MeSH terms
- Dependovirus, Adenosine Triphosphate, Animals, Electroretinography, Gene Expression Regulation, Genetic Vectors, Mice, Inbred DBA, NADH Dehydrogenase, Retinal Ganglion Cells, Visual Acuity, Gene Transfer Techniques, Microscopy, Confocal, Thy-1 Antigens, Fluorescent Antibody Technique, Indirect, Electron Transport Complex I, Green Fluorescent Proteins, Mice
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