Intravitreal injection of AAV2 transduces macaque inner retina
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PURPOSE: Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection in several species. However, results in nonprimates may not be predictive of transduction in the human inner retina, because of differences in eye size and the specialized morphology of the high-acuity human fovea. This was a study of inner retina transduction in the macaque, a primate with ocular characteristics most similar to that of humans. METHODS: In vivo imaging and histology were used to examine GFP expression in the macaque inner retina after intravitreal injection of AAV vectors containing five distinct promoters. RESULTS: AAV2 produced pronounced GFP expression in inner retinal cells of the fovea, no expression in the central retina beyond the fovea, and variable expression in the peripheral retina. AAV2 vector incorporating the neuronal promoter human connexin 36 (hCx36) transduced ganglion cells within a dense annulus around the fovea center, whereas AAV2 containing the ubiquitous promoter hybrid cytomegalovirus (CMV) enhancer/chicken-β-actin (CBA) transduced both Müller and ganglion cells in a dense circular disc centered on the fovea. With three shorter promoters--human synapsin (hSYN) and the shortened CBA and hCx36 promoters (smCBA and hCx36sh)--AAV2 produced visible transduction, as seen in fundus images, only when the retina was altered by ganglion cell loss or enzymatic vitreolysis. CONCLUSIONS: The results in the macaque suggest that intravitreal injection of AAV2 would produce high levels of gene expression at the human fovea, important in retinal gene therapy, but not in the central retina beyond the fovea.
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IVT AAV delivery provides significant transgene expression in the ganglion cell layer, particularly in retinal ganglion cells.
“AAV vector delivery via intravitreal (IVT) injection is a minimally invasive procedure that offers the potential for broad inner retinal transduction, providing significant transgene expression in the ganglion cell layer (GCL) (10, 14–17), and in particular in retinal ganglion cells (RGCs) (17–20).”
From Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses (2026) · cites this paper as [17]
Intravitreal injection of rAAV2 with a ubiquitous promoter infects Müller glial cells and ganglion cells.
“Intravitreal injection (ubiquitous promoter): rAAV2 infects Müller glial cells and ganglion cells [322].”
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 [322]
Current AAVs in clinical testing mediate transduction of retinal ganglion cells (RGCs) in the macular "ring," Müller glia, and sparse PRs adjacent to large blood vessels, some foveal cones, and non-neuronal cells of the ciliary body.
“Current AAVs in clinical testing mediate transduction of retinal ganglion cells (RGCs) in the macular “ring,” Müller glia, and sparse PRs adjacent to large blood vessels, some foveal cones, and non-neuronal cells of the ciliary body.121, 122, 123, 124”
From Current clinical applications of in vivo gene therapy with AAVs (2021) · cites this paper as [121]
AAV2 or AAV2 variants are often used for intravitreal injection, while AAV8 is commonly used for subretinal injection.
“For example, AAV2 or AAV2 variants are often used to for intravitreal injection62–64, while AAV8 is commonly used for subretinal injection65,66.”
From An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species (2024) · cites this paper as [64]
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Cites
Topography of ganglion cells in human retina
Curcio, C. A., & Allen, K. A. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.903000103 · Cited by 1,849 · see citing works
Summerford, C., & Samulski, R. J. (1998) · Journal of Virology · doi:10.1128/jvi.72.2.1438-1445.1998 · Cited by 1,409 · see citing works
Zolotukhin, S., Byrne, B. J., Mason, E. G., Zolotukhin, I., Potter, M., Chesnut, K. A., Summerford, C., Samulski, R. J., & Muzyczka, N. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300938 · Cited by 1,317 · see citing works
(1984) · PubMed · Cited by 1,200 · see citing works
Gene therapy using adeno-associated virus vectors
Daya, S., & Berns, K. I. (2008) · Clinical Microbiology Reviews · doi:10.1128/cmr.00008-08 · Cited by 926 · see citing works
Maguire, 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
αVβ5 integrin: a co-receptor for adeno-associated virus type 2 infection
Summerford, C., Bartlett, J. S., & Samulski, R. J. (1999) · Nature Medicine · doi:10.1038/4768 · Cited by 711 · see citing works
Quantitative analysis of the packaging capacity of recombinant adeno-associated virus
Dong, J.-Y., Fan, P.-D., & Frizzell, R. A. (1996) · Human Gene Therapy · doi:10.1089/hum.1996.7.17-2101 · Cited by 583 · see citing works
Webvision: The Organization of the Retina and Visual System
Kolb, H., Fernández, E., & Nelson, R. (1995) · Cited by 544 · see citing works
Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors
Bartlett, J. S., Wilcher, R., & Samulski, R. J. (2000) · Journal of Virology · doi:10.1128/jvi.74.6.2777-2785.2000 · Cited by 532 · see citing works
Perry, V. H., & Cowey, A. (1985) · Vision Research · doi:10.1016/0042-6989(85)90004-5 · Cited by 498 · see citing works
Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2
Qing, K., Mah, C., Hansen, J., Zhou, S., Dwarki, V., & Srivastava, A. (1999) · Nature Medicine · doi:10.1038/4758 · Cited by 443 · see citing works
Kügler, S., Kilic, E., & Bähr, M. (2003) · Gene Therapy · doi:10.1038/sj.gt.3301905 · Cited by 412 · 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
Inner limiting membrane barriers to aav-mediated retinal transduction from the vitreous
Dalkara, D., Kolstad, K. D., Caporale, N., Visel, M., Klimczak, R. R., Schaffer, D. V., & Flannery, J. G. (2009) · Molecular Therapy · doi:10.1038/mt.2009.181 · Cited by 357 · see citing works
Self-citationGene therapy for red–green colour blindness in adult primates
Mancuso, K., Hauswirth, W. W., Li, Q., Connor, T. B., Kuchenbecker, J. A., Mauck, M. C., Jay Neitz, A., & Neitz, M. (2009) · Nature · doi:10.1038/nature08401 · Cited by 349 · see citing works
Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis)
Snodderly, D. M., Weinhaus, R., & Choi, J. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-04-01169.1992 · Cited by 337 · see citing works
Cortical magnification factor and the ganglion cell density of the primate retina
Wässle, H., Grünert, U., Röhrenbeck, J., & Boycott, B. B. (1989) · Nature · doi:10.1038/341643a0 · Cited by 332 · see citing works
Retinal ganglion cell density and cortical magnification factor in the primate
Wässle, H., Grünert, U., Röhrenbeck, J., & Boycott, B. B. (1990) · Vision Research · doi:10.1016/0042-6989(90)90166-i · Cited by 330 · see citing works
Selective and Rapid Uptake of Adeno-Associated Virus Type 2 in Brain
Bartlett, J. S., Samulski, R. J., & McCown, T. J. (1998) · Human Gene Therapy · doi:10.1089/hum.1998.9.8-1181 · Cited by 301 · see citing works
Functional and cortical adaptations to central vision loss
Cheung, S. H., & Legge, G. E. (2005) · Visual Neuroscience · doi:10.1017/s0952523805222071 · Cited by 206 · see citing works
Anatomy of macaque fovea and spatial densities of neurons in foveal representation
Schein, S. (1988) · The Journal of Comparative Neurology · doi:10.1002/cne.902690403 · Cited by 194 · see citing works
(2008) · PubMed Central · Cited by 183 · see citing works
Posterior Vitreous Detachment Induced by Microplasmin
Gandorfer, A., Rohleder, M., Sethi, C. S., et al. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.03-0930 · Cited by 180 · see citing works
In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells
Gray, D. C., Merigan, W. H., Wolfing, J. I., Gee, B. P., Porter, J., Dubra, A., Twietmeyer, T. H., Ahmad, K., Tumbar, R., Reinholz, F. N., et al. (2006) · Optics Express · doi:10.1364/oe.14.007144 · Cited by 178 · see citing works
Self-citationVisual optics and retinal cone topography in the common marmoset (Callithrix jacchus)
Troilo, D., Rowland, H. C., & Judge, S. J. (1993) · Vision Research · doi:10.1016/0042-6989(93)90038-x · Cited by 165 · see citing works
Kügler, S., Lingor, P., Schöll, U., Zolotukhin, S., & Bähr, M. (2003) · Virology · doi:10.1016/s0042-6822(03)00162-4 · Cited by 153 · see citing works
Versatility of AAV vectors for retinal gene transfer
Surace, E. M., & Auricchio, A. (2007) · Vision Research · doi:10.1016/j.visres.2007.07.027 · Cited by 145 · see citing works
Hellström, M., Ruitenberg, M. J., Pollett, M. A., Ehlert, E. M. E., Twisk, J., Verhaagen, J., & Harvey, A. R. (2009) · Gene Therapy · doi:10.1038/gt.2008.178 · Cited by 142 · see citing works
Glia Cells of the Monkey Retina—II. Müller Cells
Distler, C., & Dreher, Z. (1996) · Vision Research · doi:10.1016/0042-6989(96)00005-3 · Cited by 132 · see citing works
Adeno-Associated Virus Gene Transfer to Mouse Retina
Ali, R. R., Reichel, M. B., de Alwis, M., Kanuga, N., Kinnon, C., Levinsky, R. J., Hunt, D. M., Bhattacharya, S. S., & Thrasher, A. J. (1998) · Human Gene Therapy · doi:10.1089/hum.1998.9.1-81 · Cited by 124 · see citing works
AAV-mediated gene therapy for retinal disorders: from mouse to man
Buch, P. K., Bainbridge, J. W., & Ali, R. R. (2008) · Gene Therapy · doi:10.1038/gt.2008.66 · Cited by 122 · see citing works
Tan, M. H., Smith, A. J., Pawlyk, B. S., Xu, X., Liu, X., Bainbridge, J. W., Basche, M., McIntosh, J., Tran, H. V., Nathwani, A. C., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp133 · Cited by 119 · see citing works
Gene therapy and transplantation in CNS repair: The visual system
Harvey, A. R., Hu, Y. J., Leaver, S. G., Mellough, C., Park, K. K., Verhaagen, J., Plant, G. W., & Cui, Q. (2006) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2006.07.002 · Cited by 110 · see citing works
Evaluation of AAV-Mediated Expression of Chop2-GFP in the Marmoset Retina
Ivanova, E., Hwang, G.-S., Pan, Z., & Troilo, D. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-5389 · Cited by 105 · see citing works
Normal ocular development in young rhesus monkeys (Macaca mulatta)
Qiao-Grider, Y., Hung, L., Kee, C., Ramamirtham, R., & Smith, E. L., III (2007) · Vision Research · doi:10.1016/j.visres.2007.01.025 · Cited by 103 · see citing works
Human Evolution. An Illustrated Introduction
Susman, R. L. (1986) · Journal of Human Evolution · doi:10.1016/s0047-2484(86)80023-9 · Cited by 102 · see citing works
Cell density ratios in a foveal patch in macaque retina
Ahmad, K. M., Klug, K., Herr, S., Sterling, P., & Schein, S. (2003) · Visual Neuroscience · doi:10.1017/s0952523803202091 · Cited by 101 · see citing works
Grünert, U., Greferath, U., Boycott, B. B., & Wässle, H. (1993) · Vision Research · doi:10.1016/0042-6989(93)90052-x · Cited by 100 · see citing works
Fitzsimons, H. L., Bland, R. J., & During, M. J. (2002) · Methods · doi:10.1016/s1046-2023(02)00227-x · Cited by 99 · see citing works
Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives
Rolling, F. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302366 · Cited by 90 · see citing works
Human evolution: An illustrated introduction
Lewin, R. A. (1984) · Cited by 86 · see citing works
Nerve fiber layer of the macaque retina: retinotopic organization.
Ogden, T. E. (1983) · PubMed · Cited by 74 · see citing works
Recovery from form-deprivation myopia in rhesus monkeys.
Qiao-Grider, Y., Hung, L.-F., Kee, C., Ramamirtham, R., & Smith, E. L. (2004) · Investigative Ophthalmology and Visual Science · doi:10.1167/iovs.04-0080 · Cited by 72 · see citing works
Lebherz, C., Maguire, A. M., Auricchio, A., Tang, W., Alemán, T. S., Wei, Z., Grant, R. L., Cideciyan, A. V., Jacobson, S. G., Wilson, J. M., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.4.1141 · Cited by 68 · see citing works
Organization of the Adult Primate Fovea
Hendrickson, A. E. (2005) · Springer eBooks · doi:10.1007/3-540-26977-0_1 · Cited by 67 · see citing works
In Vivo Imaging of Microscopic Structures in the Rat Retina
Geng, Y., Greenberg, K. P., Wolfe, R., Gray, D. C., Hunter, J. J., Dubra, A., Flannery, J. G., Williams, D. R., & Porter, J. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-3675 · Cited by 65 · see citing works
Self-citationChanges in adeno-associated virus-mediated gene delivery in retinal degeneration
Kolstad, K. D., Dalkara, D., Guerin, K., Visel, M., Hoffmann, N., Schaffer, D. V., & Flannery, J. G. (2010) · Human Gene Therapy · doi:10.1089/hum.2009.194 · Cited by 63 · see citing works
Self-citationIn Vivo Imaging of the Fine Structure of Rhodamine-Labeled Macaque Retinal Ganglion Cells
Gray, D. C., Wolfe, R., Gee, B. P., et al. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0605 · Cited by 61 · see citing works
Self-citationA four-surface schematic eye of macaque monkey obtained by an optical method
Lapuerta, P., & Schein, S. J. (1995) · Vision Research · doi:10.1016/0042-6989(94)00320-l · Cited by 59 · see citing works
Histological measurement of retinal nerve fibre layer thickness
Frenkel, S., Morgan, J. P., & Blumenthal, E. Z. (2004) · Eye · doi:10.1038/sj.eye.6701569 · Cited by 59 · see citing works
The Response to Visual Form Deprivation Differs with Age in Marmosets
Troilo, D., & Nickla, D. L. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-1422 · Cited by 56 · see citing works
Lebherz, C., Auricchio, A., Maguire, A. M., Rivera, V. M., Tang, W., Grant, R. L., Clackson, T., Bennett, J., & Wilson, J. M. (2005) · Human Gene Therapy · doi:10.1089/hum.2005.16.178 · Cited by 53 · see citing works
Axial Length, Myopia, and the Severity of Lens Opacity at the Time of Cataract Surgery
Kubo, E. (2006) · Archives of Ophthalmology · doi:10.1001/archopht.124.11.1586 · Cited by 51 · see citing works
Nerve fiber layer of the macaque retina: Retinotopic organization
Minckler, D. S. (1983) · Survey of Ophthalmology · doi:10.1016/0039-6257(83)90089-9 · Cited by 39 · see citing works
AAV-Mediated Gene Therapy for Retinal Disorders in Large Animal Models
Stieger, K., Lhériteau, E., Moullier, P., & Rolling, F. (2009) · ILAR Journal · doi:10.1093/ilar.50.2.206 · Cited by 37 · see citing works
Facts and Figures Concerning the Human Retina
Kolb, H. (1995) · Europe PMC (PubMed Central) · Cited by 29 · see citing works
Visual Acuity and the Cone Cell Distribution of the Retina
Harrison, E. R. (1953) · British Journal of Ophthalmology · doi:10.1136/bjo.37.9.538 · Cited by 16 · see citing works
Infectious Entry Pathway of Adeno-Associated Virus and Adeno-Associated Virus Vectors
Bartlett, J. S., Samulski, R. J., & Wilcher, R. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/wpm7-c313 · Cited by 16 · see citing works
Tan, M. H., Smith, A. J., Pawlyk, B., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp540 · Cited by 15 · see citing works
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Dalkara, 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 · see citing works
Self-citationCurrent 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 · see citing works
Jacobson, S. G. (2012) · Archives of Ophthalmology · doi:10.1001/archophthalmol.2011.298 · Cited by 639 · 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
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
Heier, J. S., Kherani, S., Desai, S., Dugel, P., Kaushal, S., Cheng, S. H., Delacono, C., Purvis, A., Richards, S., Le-Halpere, A., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30979-0 · Cited by 229 · 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
Early and late stage gene therapy interventions for inherited retinal degenerations
Botto, C., Rucli, M., Tekinsoy, M. D., Pulman, J., Sahel, J.-A., & Dalkara, D. (2022) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100975 · Cited by 190 · see citing works
Self-citationRoska, B., & Sahel, J.-A. (2018) · Nature · doi:10.1038/s41586-018-0076-4 · Cited by 161 · see citing works
Kotterman, M. A., Yin, L., Strazzeri, J. M., Flannery, J. G., Merigan, W. H., & Schaffer, D. V. (2015) · Gene Therapy · doi:10.1038/gt.2014.115 · Cited by 169 · see citing works
Self-citationTargeting photoreceptors via intravitreal delivery using novel, capsid-mutated AAV vectors
Kay, C. N., Ryals, R. C., Aslanidi, G. V., Min, S. H., Ruan, Q., Sun, J., Dyka, F. M., Kasuga, D., Ayala, A. E., Van Vliet, K., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062097 · Cited by 168 · see citing works
Evaluation of Dose and Safety of AAV7m8 and AAV8BP2 in the Non-Human Primate Retina
Ramachandran, P. S., Lee, V., Wei, Z., Song, J. Y., Casal, G., Cronin, T., Willett, K., Huckfeldt, R., Morgan, J. I. W., Aleman, T. S., et al. (2017) · Human Gene Therapy · doi:10.1089/hum.2016.111 · Cited by 147 · see citing works
Noninvasive gene delivery to foveal cones for vision restoration
Khabou, H., Garita-Hernandez, M., Chaffiol, A., Reichman, S., Jaillard, C., Brazhnikova, E., Bertin, S., Forster, V., Desrosiers, M., Winckler, C., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.96029 · Cited by 124 · see citing works
Self-citationBoye, S. E., Alexander, J. J., Boye, S. L., Witherspoon, C. D., Sandefer, K. J., Conlon, T. J., Erger, K., Sun, J., Ryals, R., Chiodo, V. A., et al. (2012) · Human Gene Therapy · doi:10.1089/hum.2012.125 · Cited by 117 · see citing works
In vivo–directed evolution of adeno-associated virus in the primate retina
Byrne, L. C., Day, T. P., Visel, M., Strazzeri, J. A., Fortuny, C., Dalkara, D., Merigan, W. H., Schaffer, D. V., & Flannery, J. G. (2020) · JCI Insight · doi:10.1172/jci.insight.135112 · Cited by 104 · see citing works
Self-citationNanoparticle-based technologies for retinal gene therapy
Adijanto, J., & Naash, M. I. (2015) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2014.12.028 · Cited by 107 · see citing works
Takahashi, K., Igarashi, T., Miyake, K., Kobayashi, M., Yaguchi, C., Iijima, O., Yamazaki, Y., Katakai, Y., Miyake, N., Kameya, S., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2016.10.008 · Cited by 99 · see citing works
“Although retinal transduction through intravitreal AAV administration has been reported for the primate retina, the transduction efficiency was lower than into the mouse retina.(12) It was reported that the vitreous and internal limiting membrane (ILM) form a barrier to transduction.”
BackgroundBuck, T., & Wijnholds, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124197 · Cited by 92 · see citing works
“Intravitreal injection (ubiquitous promoter): rAAV2 infects Müller glial cells and ganglion cells [322].”
BackgroundGene therapy for retinal disease
McClements, M. E., & MacLaren, R. E. (2013) · Translational Research · doi:10.1016/j.trsl.2012.12.007 · Cited by 80 · see citing works
Timmers, A. M., Newmark, J. A., Turunen, H. T., Farivar, T., Liu, J., Song, C., Ye, G.-J., Pennock, S., Gaskin, C., Knop, D. R., et al. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.144 · Cited by 77 · see citing works
Hickey, D. G., Edwards, T. L., Barnard, A. R., Singh, M. S., de Silva, S. R., McClements, M. E., Flannery, J. G., Hankins, M. W., & MacLaren, R. E. (2017) · Gene Therapy · doi:10.1038/gt.2017.85 · Cited by 72 · see citing works
Self-citationThe future of retinal gene therapy: evolving from subretinal to intravitreal vector delivery
Ross, M., & Ofri, R. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.306063 · Cited by 67 · see citing works
“It is therefore expected (and indeed confirmed) that IVT-injected vectors would transduce inner retinal layers to a higher extent than outer retinal layers, even though most treatments are aimed at the latter (Ali et al., 1998; Li et al., 2008; Yin et al., 2011; Dalkara et al., 2013; Ramachandran et al., 2017; Dias et…”
BackgroundYe, G.-J., Budzynski, E., Sonnentag, P., Nork, T. M., Miller, P. E., Sharma, A. K., Ver Hoeve, J. N., Smith, L. M., Arndt, T., Calcedo, R., et al. (2016) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2015.164 · Cited by 64 · see citing works
Gene therapy for age-related macular degeneration
Moore, N. A., Bracha, P., Hussain, R. M., Morral, N., & Ciulla, T. A. (2017) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2017.1356817 · Cited by 63 · see citing works
Carvalho, L. S., Xiao, R., Wassmer, S. J., Langsdorf, A., Zinn, E., Pacouret, S., Shah, S., Comander, J. I., Kim, L. A., Lim, L., et al. (2018) · Human Gene Therapy · doi:10.1089/hum.2017.154 · Cited by 63 · see citing works
Imaging light responses of foveal ganglion cells in the living macaque eye
Yin, L., Masella, B., Dalkara, D., Zhang, J., Flannery, J. G., Schaffer, D. V., Williams, D. R., & Merigan, W. H. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.4438-13.2014 · Cited by 54 · see citing works
Self-citationWoodard, K. T., Liang, K. J., Bennett, W. C., & Samulski, R. J. (2016) · Journal of Virology · doi:10.1128/jvi.01568-16 · Cited by 59 · see citing works
Charbel Issa, P., De Silva, S. R., Lipinski, D. M., Singh, M. S., Mouravlev, A., You, Q., Barnard, A. R., Hankins, M. W., During, M. J., & MacLaren, R. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060361 · Cited by 53 · see citing works
AAV‐mediated gene delivery in Dp71‐null mouse model with compromised barriers
Vacca, O., Darche, M., Schaffer, D. V., Flannery, J. G., Sahel, J., Rendon, A., & Dalkara, D. (2014) · Glia · doi:10.1002/glia.22617 · Cited by 48 · see citing works
Self-citationEvaluation of AAV-DJ vector for retinal gene therapy
Katada, Y., Kobayashi, K., Tsubota, K., & Kurihara, T. (2019) · PeerJ · doi:10.7717/peerj.6317 · Cited by 46 · see citing works
An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species
Luo, S., Jiang, H., Li, Q., Qin, Y., Yang, S., Li, J., Xu, L., Gou, Y., Zhang, Y., Liu, F., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48221-4 · Cited by 39 · see citing works
Focused Update on AAV-Based Gene Therapy Clinical Trials for Inherited Retinal Degeneration
Fuller-Carter, P. I., Basiri, H., Harvey, A. R., & Carvalho, L. S. (2020) · BioDrugs · doi:10.1007/s40259-020-00453-8 · Cited by 41 · see citing works
Engineered Capsids for Efficient Gene Delivery to the Retina and Cornea
Frederick, A., Sullivan, J., Liu, L., Adamowicz, M., Lukason, M., Raymer, J., Luo, Z., Jin, X., Rao, K. N., & O'Riordan, C. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.070 · Cited by 35 · see citing works
Boyd, R. F., Boye, S. L., Conlon, T. J., Erger, K. E., Sledge, D. G., Langohr, I. M., Hauswirth, W. W., Komáromy, A. M., Boye, S. E., Petersen-Jones, S. M., et al. (2016) · Gene Therapy · doi:10.1038/gt.2016.31 · Cited by 37 · 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
Teo, K. Y. C., Lee, S. Y., Barathi, A. V., Tun, S. B. B., Tan, L., & Constable, I. J. (2018) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.18-24333 · Cited by 33 · see citing works
Cehajic-Kapetanovic, J., Milosavljevic, N., Bedford, R. A., Lucas, R. J., & Bishop, P. N. (2018) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2017.12.002 · Cited by 30 · see citing works
Novel AAV44.9-Based Vectors Display Exceptional Characteristics for Retinal Gene Therapy
Boye, S. L., Choudhury, S., Crosson, S., Di Pasquale, G., Afione, S., Mellen, R., Makal, V., Calabro, K. R., Fajardo, D., Peterson, J., et al. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.04.002 · Cited by 29 · see citing works
Lipinski, D. M., Barnard, A. R., Issa, P. C., Singh, M. S., De Silva, S. R., Trabalza, A., Eleftheriadou, I., Ellison, S. M., Mazarakis, N. D., & MacLaren, R. E. (2014) · Human Gene Therapy · doi:10.1089/hum.2013.009 · Cited by 24 · see citing works
Calton, M. A., Croze, R. H., Burns, C., Beliakoff, G., Vazin, T., Szymanski, P., Schmitt, C., Klein, A., Leong, M., Quezada, M., et al. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.14.1 · Cited by 21 · see citing works
“38,43”
Self-citationKotterman, M., Beliakoff, G., Croze, R., Vazin, T., Schmitt, C., Szymanski, P., Leong, M., Quezada, M., Holt, J., Barglow, K., et al. (2021) · doi:10.1101/2021.06.24.449775 · Cited by 20 · see citing works
Self-citationRetina transduction by rAAV2 after intravitreal injection: Comparison between mouse and rat
Dias, M. S., Araujo, V. G., Vasconcelos, T., Li, Q., Hauswirth, W. W., Linden, R., & Petrs-Silva, H. (2019) · Gene Therapy · doi:10.1038/s41434-019-0100-9 · Cited by 17 · see citing works
Neutralisation of adeno-associated virus transduction by human vitreous humour
Andrzejewski, S., Moyle, P. M., Stringer, B. W., Steel, J. C., & Layton, C. J. (2021) · Gene Therapy · doi:10.1038/s41434-020-0162-8 · Cited by 10 · see citing works
Importance of nonhuman primates as a model system for gene therapy development in ophthalmology
Wozar, F., Seitz, I., Reichel, F., & Fischer, M. D. (2022) · Klinische Monatsblätter für Augenheilkunde · doi:10.1055/a-1777-5033 · Cited by 6 · see citing works
Costa-Verdera, H., Jamwal, D., Fabyanic, E., Hippen, A., Salvatore, M., Du, A., Majowicz, A., Markusic, D., Chatterton, J. E., Haurigot, V., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1799327 · Cited by 2 · see citing works
“…delivery via intravitreal (IVT) injection is a minimally invasive procedure that offers the potential for broad inner retinal transduction, providing signi fi cant transgene expression in the ganglion cell layer (GCL) (10, 14 – 17), and in particular in retinal ganglion cells (RGCs) (17 – 20).”
- Authors
- Yin, L., Greenberg, K., Hunter, J. J., Dalkara, D., Kolstad, K. D., Masella, B. D., Wolfe, R., Visel, M., Stone, D., Libby, R. T., DiLoreto, D., Schaffer, D., Flannery, J., Williams, D. R., & Merigan, W. H.
- Affiliations
- From the Flaum Eye Institute, the 2Center for Visual Science,
- the Helen Wills Neuroscience Institute and the Departments of 4Molecular and Cell Biology, 5Vision Science, and
- the Helen Wills Neuroscience Institute and
- University of Rochester (US)
- the Center for Visual Science,
- University of California, Berkeley (US)
- From the Flaum Eye Institute,
- Corresponding author
- Yin, Lu
- Greenberg, Kenneth
- Hunter, Jennifer J.
- Dalkara, Deniz
- Kolstad, Kathleen D.
- Masella, Benjamin D.
- Wolfe, Robert
- Visel, Meike
- Stone, Daniel
- Libby, Richard T.
- DiLoreto, David
- Schaffer, David
- Flannery, John
- Williams, David R.
- Merigan, William H.
- ORCID
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2011-04-25
- Volume
- 52
- Issue
- 5
- Pages
- 2775
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC3088562
- OpenAlex
- W1992246699
- Cited by
- 212
- References
- 60
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 15 · 2023: 9 · 2022: 21 · 2021: 18 · 2020: 19 · 2019: 14 · 2018: 10 · 2017: 21 · 2016: 11 · 2015: 17 · 2014: 13 · 2013: 15 · 2012: 6
- FWCI
- 7.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9876783)
- Research to Prevent Blindness
- University of Rochester
- National Institutes of Health (EY001319)
- Center for Visual Science
- National Heart, Lung, and Blood Institute (R01HL081527)
- National Eye Institute (EY 07125, EY-019375, EY-001319, PN2EY018241, R01EY014375, R21EY019375, EY-014375, T32EY007125, P30EY001319)
- 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 › Retinal Diseases and Treatments
- Keywords
- AAV2, intravitreal injection, macaque retina, fovea, retinal gene therapy, ganglion cells, Müller cells, cytomegalovirus promoter, chicken beta-actin promoter, synapsin promoter, promoter comparison, ganglion cell loss, vitreolysis
- MeSH terms
- Gap Junction delta-2 Protein, Actins, Dependovirus, Animals, Axons, Genetic Vectors, Macaca, Retinal Ganglion Cells, Transduction, Genetic, Gene Expression, Synapsins, Microglia, Connexins, Genes, Reporter, Microscopy, Confocal, Green Fluorescent Proteins, Intravitreal Injections
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