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Current Gene Therapy

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ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

Review Article

Optogenetics: Illuminating the Future of Hearing Restoration and Understanding Auditory Perception

Author(s): Namit Kant Singh*, Balaji Ramamourthy, Neemu Hage and Krishna Medha Kappagantu

Volume 24, Issue 3, 2024

Published on: 03 January, 2024

Page: [208 - 216] Pages: 9

DOI: 10.2174/0115665232269742231213110937

Price: $65

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Abstract

Hearing loss is a prevalent sensory impairment significantly affecting communication and quality of life. Traditional approaches for hearing restoration, such as cochlear implants, have limitations in frequency resolution and spatial selectivity. Optogenetics, an emerging field utilizing light-sensitive proteins, offers a promising avenue for addressing these limitations and revolutionizing hearing rehabilitation. This review explores the methods of introducing Channelrhodopsin- 2 (ChR2), a key light-sensitive protein, into cochlear cells to enable optogenetic stimulation. Viral- mediated gene delivery is a widely employed technique in optogenetics. Selecting a suitable viral vector, such as adeno-associated viruses (AAV), is crucial in efficient gene delivery to cochlear cells. The ChR2 gene is inserted into the viral vector through molecular cloning techniques, and the resulting viral vector is introduced into cochlear cells via direct injection or round window membrane delivery. This allows for the expression of ChR2 and subsequent light sensitivity in targeted cells. Alternatively, direct cell transfection offers a non-viral approach for ChR2 delivery. The ChR2 gene is cloned into a plasmid vector, which is then combined with transfection agents like liposomes or nanoparticles. This mixture is applied to cochlear cells, facilitating the entry of the plasmid DNA into the target cells and enabling ChR2 expression. Optogenetic stimulation using ChR2 allows for precise and selective activation of specific neurons in response to light, potentially overcoming the limitations of current auditory prostheses. Moreover, optogenetics has broader implications in understanding the neural circuits involved in auditory processing and behavior. The combination of optogenetics and gene delivery techniques provides a promising avenue for improving hearing restoration strategies, offering the potential for enhanced frequency resolution, spatial selectivity, and improved auditory perception.

Graphical Abstract

[1]
Casale J, Kandle PF, Murray IV, Murr N. Physiology, cochlear function. StatPearls. Treasure Island, FL: StatPearls Publishing 2023.
[2]
Krogmann RJ, Al Khalili Y. Cochlear implants. StatPearls. Treasure Island, FL: StatPearls Publishing 2023.
[3]
Kitcher SR, Weisz CJC. Shedding light on optical cochlear implant progress. EMBO Mol Med 2020; 12(8): e12620.
[http://dx.doi.org/10.15252/emmm.202012620] [PMID: 32715629]
[4]
Dieter A, Keppeler D, Moser T. Towards the optical cochlear implant: Optogenetic approaches for hearing restoration. EMBO Mol Med 2020; 12(4): e11618.
[http://dx.doi.org/10.15252/emmm.201911618] [PMID: 32227585]
[5]
Hernandez VH, Gehrt A, Reuter K, et al. Optogenetic stimulation of the auditory pathway. J Clin Invest 2014; 124(3): 1114-29.
[http://dx.doi.org/10.1172/JCI69050] [PMID: 24509078]
[6]
Keppeler D, Merino RM, Morena D, et al. Ultrafast optogenetic stimulation of the auditory pathway by targeting-optimized Chronos. EMBO J 2018; 37(24): e99649.
[http://dx.doi.org/10.15252/embj.201899649] [PMID: 30396994]
[7]
Dieter A, Duque-Afonso CJ, Rankovic V, Jeschke M, Moser T. Near physiological spectral selectivity of cochlear optogenetics. Nat Commun 2019; 10(1): 1962.
[http://dx.doi.org/10.1038/s41467-019-09980-7] [PMID: 31036812]
[8]
Liu CT. Auditory responses evoked by optical stimulation on the optogenetic-infected cochlear neurons in the guinea pigs. bioRxiv 2020.
[9]
Kim WB, Cho JH. Encoding of discriminative fear memory by input-specific LTP in the amygdala. Neuron 2017; 95(5): 1129-1146.e5.
[http://dx.doi.org/10.1016/j.neuron.2017.08.004] [PMID: 28823727]
[10]
Kozin ED, Darrow KN, Hight AE, et al. Direct visualization of the murine dorsal cochlear nucleus for optogenetic stimulation of the auditory pathway. J Vis Exp 2015; (95): 52426.
[PMID: 25650555]
[11]
Ritter E, Stehfest K, Berndt A, Hegemann P, Bartl FJ. Monitoring light-induced structural changes of channelrhodopsin-2 by uv-visible and fourier transform infrared spectroscopy. J Biol Chem 2008; 283(50): 35033-41.
[http://dx.doi.org/10.1074/jbc.M806353200] [PMID: 18927082]
[12]
Lórenz-Fonfría VA, Heberle J. Channelrhodopsin unchained: Structure and mechanism of a light-gated cation channel. Biochim Biophys Acta Bioenerg 2014; 1837(5): 626-42.
[http://dx.doi.org/10.1016/j.bbabio.2013.10.014]
[13]
Wang H, Sugiyama Y, Hikima T, et al. Molecular determinants differentiating photocurrent properties of two channelrhodopsins from chlamydomonas. J Biol Chem 2009; 284(9): 5685-96.
[http://dx.doi.org/10.1074/jbc.M807632200] [PMID: 19103605]
[14]
Lin JY, Lin MZ, Steinbach P, Tsien RY. Characterization of engineered channelrhodopsin variants with improved properties and kinetics. Biophys J 2009; 96(5): 1803-14.
[http://dx.doi.org/10.1016/j.bpj.2008.11.034] [PMID: 19254539]
[15]
Lin JY. A user’s guide to channelrhodopsin variants: Features, limitations and future developments. Exp Physiol 2011; 96(1): 19-25.
[http://dx.doi.org/10.1113/expphysiol.2009.051961] [PMID: 20621963]
[16]
Kleinlogel S, Feldbauer K, Dempski RE, et al. Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh. Nat Neurosci 2011; 14(4): 513-8.
[http://dx.doi.org/10.1038/nn.2776] [PMID: 21399632]
[17]
Grubb MS, Burrone J. Channelrhodopsin-2 localised to the axon initial segment. PLoS One 2010; 5(10): e13761.
[http://dx.doi.org/10.1371/journal.pone.0013761] [PMID: 21048938]
[18]
Diester I, Kaufman MT, Mogri M, et al. An optogenetic toolbox designed for primates. Nat Neurosci 2011; 14(3): 387-97.
[http://dx.doi.org/10.1038/nn.2749] [PMID: 21278729]
[19]
Nagel G, Brauner M, Liewald JF, Adeishvili N, Bamberg E, Gottschalk A. Light activation of channelrhodopsin-2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses. Curr Biol 2005; 15(24): 2279-84.
[http://dx.doi.org/10.1016/j.cub.2005.11.032] [PMID: 16360690]
[20]
Sineshchekov OA, Govorunova EG, Wang J, Li H, Spudich JL. Intramolecular proton transfer in channelrhodopsins. Biophys J 2013; 104(4): 807-17.
[http://dx.doi.org/10.1016/j.bpj.2013.01.002] [PMID: 23442959]
[21]
Prigge M, Schneider F, Tsunoda SP, et al. Color-tuned channelrhodopsins for multiwavelength optogenetics. J Biol Chem 2012; 287(38): 31804-12.
[http://dx.doi.org/10.1074/jbc.M112.391185] [PMID: 22843694]
[22]
Sineshchekov OA, Li H, Govorunova EG, Spudich JL. Photochemical reaction cycle transitions during anion channelrhodopsin gating. Proceedings of the National Academy of Sciences 2016; 113(14): E1993-2000.
[http://dx.doi.org/10.1073/pnas.1525269113]
[23]
Landegger LD, Pan B, Askew C, et al. A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear. Nat Biotechnol 2017; 35(3): 280-4.
[http://dx.doi.org/10.1038/nbt.3781] [PMID: 28165475]
[24]
Mei Y, Zhang F. Molecular tools and approaches for optogenetics. Biol Psychiatry 2012; 71(12): 1033-8.
[http://dx.doi.org/10.1016/j.biopsych.2012.02.019] [PMID: 22480664]
[25]
Poletti V, Mavilio F. Designing lentiviral vectors for gene therapy of genetic Diseases. Viruses 2021; 13(8): 1526.
[http://dx.doi.org/10.3390/v13081526] [PMID: 34452394]
[26]
Isgrig K, McDougald DS, Zhu J, Wang HJ, Bennett J, Chien WW. AAV2.7m8 is a powerful viral vector for inner ear gene therapy. Nat Commun 2019; 10(1): 427.
[http://dx.doi.org/10.1038/s41467-018-08243-1] [PMID: 30683875]
[27]
Shu Y, Tao Y, Wang Z, et al. Identification of adeno-associated viral vectors that target neonatal and adult mammalian inner ear cell subtypes. Hum Gene Ther 2016; 27(9): 687-99.
[http://dx.doi.org/10.1089/hum.2016.053] [PMID: 27342665]
[28]
Tan F, Chu C, Qi J, et al. AAV-ie enables safe and efficient gene transfer to inner ear cells. Nat Commun 2019; 10(1): 3733.
[http://dx.doi.org/10.1038/s41467-019-11687-8] [PMID: 31427575]
[29]
Kilpatrick LA, Li Q, Yang J, Goddard JC, Fekete DM, Lang H. Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear. Gene Ther 2011; 18(6): 569-78.
[http://dx.doi.org/10.1038/gt.2010.175] [PMID: 21209625]
[30]
Casey G, Askew C, Brimble MA, et al. Self-complementarity in adeno-associated virus enhances transduction and gene expression in mouse cochlear tissues. PLoS One 2020; 15(11): e0242599.
[http://dx.doi.org/10.1371/journal.pone.0242599] [PMID: 33227033]
[31]
Chien WW, McDougald DS, Roy S, Fitzgerald TS, Cunningham LL. Cochlear gene transfer mediated by adeno-associated virus: Comparison of two surgical approaches. Laryngoscope 2015; 125(11): 2557-64.
[32]
Chong ZX, Yeap SK, Ho WY. Transfection types, methods and strategies: A technical review. PeerJ 2021; 9: e11165.
[http://dx.doi.org/10.7717/peerj.11165] [PMID: 33976969]
[33]
Pichon C, Billiet L, Midoux P. Chemical vectors for gene delivery: Uptake and intracellular trafficking. Curr Opin Biotechnol 2010; 21(5): 640-5.
[http://dx.doi.org/10.1016/j.copbio.2010.07.003] [PMID: 20674331]
[34]
Zhou R, Geiger RC, Dean DA. Intracellular trafficking of nucleic acids. Expert Opin Drug Deliv 2004; 1(1): 127-40.
[http://dx.doi.org/10.1517/17425247.1.1.127] [PMID: 16296725]
[35]
Delalande A, Kotopoulis S, Postema M, Midoux P, Pichon C. Sonoporation: Mechanistic insights and ongoing challenges for gene transfer. Gene 2013; 525(2): 191-9.
[http://dx.doi.org/10.1016/j.gene.2013.03.095] [PMID: 23566843]
[36]
Boehringer S, Ruzgys P, Tamò L, et al. A new electrospray method for targeted gene delivery. Sci Rep 2018; 8(1): 4031.
[http://dx.doi.org/10.1038/s41598-018-22280-2] [PMID: 29507307]
[37]
Znamenskiy P, Zador AM. Corticostriatal neurons in auditory cortex drive decisions during auditory discrimination. Nature 2013; 497(7450): 482-5.
[http://dx.doi.org/10.1038/nature12077] [PMID: 23636333]
[38]
Hight AE, Kozin ED, Darrow K, et al. Superior temporal resolution of Chronos versus channelrhodopsin-2 in an optogenetic model of the auditory brainstem implant. Hear Res 2015; 322: 235-41.
[http://dx.doi.org/10.1016/j.heares.2015.01.004] [PMID: 25598479]
[39]
Erofeev A, Gerasimov E, Lavrova A, et al. Light stimulation parameters determine neuron dynamic characteristics. Appl Sci 2019; 9(18): 3673.
[http://dx.doi.org/10.3390/app9183673]
[40]
Garrido-Charles A, Cabré G, Gascón-Moya M, Busqué F, Alibés R, Hernando J. Nanoengineered light-harvested proteins for optogenetics and photopharmacology. ChemRxiv 2019.
[http://dx.doi.org/10.26434/chemrxiv.11424000.v1]
[41]
Sizova I, Greiner A, Awasthi M, Kateriya S, Hegemann P. Nuclear gene targeting in Chlamydomonas using engineered zinc-finger nucleases. Plant J 2013; 73(5): 873-82.
[http://dx.doi.org/10.1111/tpj.12066] [PMID: 23137232]
[42]
Broggini AC. Optogenetic stimulation reveals frequency-dependent resonance and encoding in V1 excitatory and inhibitory neurons. bioRxiv 2023.
[http://dx.doi.org/10.1101/2023.04.10.536138]
[43]
Fitch JL, Holbrook A. Modal vocal fundamental frequency of young adults. Arch Otolaryngol Head Neck Surg 1970; 92(4): 379-82.
[http://dx.doi.org/10.1001/archotol.1970.04310040067012] [PMID: 5455579]
[44]
Kalmbach A, Waters J. Modulation of high- and low-frequency components of the cortical local field potential via nicotinic and muscarinic acetylcholine receptors in anesthetized mice. J Neurophysiol 2014; 111(2): 258-72.
[http://dx.doi.org/10.1152/jn.00244.2013] [PMID: 24155009]
[45]
Hu W, Tu H, Wadman M, Li Y, Zhang D. Optogenetic therapy on cardiac vagal dysfunction-related ventricular arrhythmia in type 2 diabetes. Physiology 2023; 38(S1): 5727980.
[http://dx.doi.org/10.1152/physiol.2023.38.S1.5727980]
[46]
Adam S, Wiebeler C, Schapiro I. Structural factors determining the absorption spectrum of channelrhodopsins: A case study of the chimera C1C2. J Chem Theory Comput 2021; 17(10): 6302-13.
[http://dx.doi.org/10.1021/acs.jctc.1c00160] [PMID: 34255519]
[47]
Nagel G, Szellas T, Huhn W, Kateriya S, Adeishvili N, Berthold P. Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci 2003; 100(24): 13940-5.
[http://dx.doi.org/10.1073/pnas.1936192100]
[48]
Berthold P, Tsunoda SP, Ernst OP, Mages W, Gradmann D, Hegemann P. Channelrhodopsin-1 initiates phototaxis and photophobic responses in chlamydomonas by immediate light-induced depolarization. Plant Cell 2008; 20(6): 1665-77.
[http://dx.doi.org/10.1105/tpc.108.057919] [PMID: 18552201]
[49]
Han X, Boyden ES. Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS One 2007; 2(3): e299.
[http://dx.doi.org/10.1371/journal.pone.0000299] [PMID: 17375185]
[50]
Liang R, Yu JK, Meisner J, Liu F, Martínez TJ. Electrostatic control of photoisomerization in channelrhodopsin 2. J Am Chem Soc 2021; 143(14): 5425-37.
[http://dx.doi.org/10.1021/jacs.1c00058] [PMID: 33794085]
[51]
Seth K, Kumawat G, Vyas P. The structure and functional mechanism of eyespot in Chlamydomonas. J Basic Microbiol 2022; 62(10): 1169-78.
[52]
Yang T, Zhang W, Cheng J, et al. Formation mechanism of ion channel in channelrhodopsin-2: Molecular dynamics simulation and steering molecular dynamics simulations. Int J Mol Sci 2019; 20(15): 3780.
[http://dx.doi.org/10.3390/ijms20153780] [PMID: 31382458]
[53]
Losi A, Gardner KH, Möglich A. Blue-light receptors for optogenetics. Chem Rev 2018; 118(21): 10659-709.
[http://dx.doi.org/10.1021/acs.chemrev.8b00163] [PMID: 29984995]
[54]
Natwick DE, Collins SR. Optimized iLID membrane anchors for local optogenetic protein recruitment. ACS Synth Biol 2021; 10(5): 1009-23.
[http://dx.doi.org/10.1021/acssynbio.0c00511] [PMID: 33843200]
[55]
Guntas G, Hallett RA, Zimmerman SP, et al. Engineering an improved light-induced dimer (iLID) for controlling the localization and activity of signaling proteins. Proc Natl Acad Sci USA 2015; 112(1): 112-7.
[http://dx.doi.org/10.1073/pnas.1417910112] [PMID: 25535392]
[56]
Levskaya A, Weiner OD, Lim WA, Voigt CA. Spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature 2009; 461(7266): 997-1001.
[http://dx.doi.org/10.1038/nature08446] [PMID: 19749742]
[57]
Kennedy MJ, Hughes RM, Peteya LA, Schwartz JW, Ehlers MD, Tucker CL. Rapid blue-light–mediated induction of protein interactions in living cells. Nat Methods 2010; 7(12): 973-5.
[http://dx.doi.org/10.1038/nmeth.1524] [PMID: 21037589]
[58]
Pal AA, Benman W, Mumford TR, Chow BY, Bugaj LJ. Optogenetic clustering and membrane translocation of the BcLOV4 photoreceptor. bioRxiv 2022.
[http://dx.doi.org/10.1101/2022.12.12.520131]
[59]
Baumschlager A, Weber Y, Cánovas D, Dionisi S, Khammash M. Enhancing the performance of Magnets photosensors through directed evolution. bioRxiv 2022.
[http://dx.doi.org/10.1101/2022.11.14.516313]
[60]
Baumschlager A. Engineering light-control in biology. Front Bioeng Biotechnol 2022; 10: 901300.
[http://dx.doi.org/10.3389/fbioe.2022.901300] [PMID: 35573251]
[61]
Kawano F, Suzuki H, Furuya A, Sato M. Engineered pairs of distinct photoswitches for optogenetic control of cellular proteins. Nat Commun 2015; 6(1): 6256.
[http://dx.doi.org/10.1038/ncomms7256] [PMID: 25708714]
[62]
Benedetti L, Marvin JS, Falahati H, Guillén-Samander A, Looger LL, De Camilli P. Optimized vivid-derived magnets photodimerizers for subcellular optogenetics in mammalian cells. eLife 2020; 9: e63230.
[http://dx.doi.org/10.7554/eLife.63230] [PMID: 33174843]
[63]
Neghab HK, Soheilifar MH, Grusch M, Ortega MM, Djavid GE, Saboury AA. The state of the art of biomedical applications of optogenetics. Lasers Surg Med 2022; 54(2): 202-16.
[PMID: 34363230]
[64]
Bali B, Morena D, Mittring A, et al. Utility of red- light ultrafast optogenetic stimulation of the auditory pathway. EMBO Mol Med 2021; 13(6): e13391.
[http://dx.doi.org/10.15252/emmm.202013391] [PMID: 33960685]
[65]
Mittring A, Moser T, Huet A. Graded optogenetic activation of the auditory pathway for hearing restoration. bioRxiv 2022.
[http://dx.doi.org/10.1101/2022.09.05.506618]
[66]
Hunniford V, Kühler R, Wolf B, Keppeler D, Strenzke N, Moser T. Patient perspectives on the need for improved hearing rehabilitation: A qualitative survey study of German cochlear implant users. Front Neurosci 2023; 17: 1105562.
[http://dx.doi.org/10.3389/fnins.2023.1105562] [PMID: 36755736]
[67]
Botto C, Dalkara D, El-Amraoui A. Progress in gene editing tools and their potential for correcting mutations underlying hearing and vision loss. Front Genome Ed 2021; 3: 737632.
[http://dx.doi.org/10.3389/fgeed.2021.737632]
[68]
Ronzitti E, Zampini V, Emiliani V. Optimized Chronos sets the clock for optogenetic hearing restoration. EMBO J 2018; 37(24): e101103.
[http://dx.doi.org/10.15252/embj.2018101103] [PMID: 30509969]
[69]
Kleinlogel S, Vogl C, Jeschke M, Neef J, Moser T. Emerging approaches for restoration of hearing and vision. Physiol Rev 2020; 100(4): physrev.00035.2019.
[http://dx.doi.org/10.1152/physrev.00035.2019] [PMID: 32191560]
[70]
Murawski C, Gather MC. Emerging biomedical applications of organic light-emitting diodes. Adv Opt Mater 2021; 9(14): 2100269.
[http://dx.doi.org/10.1002/adom.202100269]

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