Brandt T, Dieterich M, Huppert D. Human senses and sensors from Aristotle to the present. Front Neurol. 2024;15.

Thouless RH. Eye and brain as factors in visual perception. Nature. 1938;142:418–21.

Google Scholar 

Keetels M, Vroomen J. Perception of synchrony between the senses. In: Murray MM, Wallace MT, editors. The neural bases of multisensory processes. Boca Raton (FL): CRC Press/Taylor & Francis; 2012.

Google Scholar 

Kaplan HJ. Anatomy and function of the eye. In: Niederkorn JY, Kaplan HJ, editors. Immune response and the eye. Basel: KARGER; 2007. pp. 4–10.

Google Scholar 

London A, Benhar I, Schwartz M. The retina as a window to the brain - From eye research to CNS disorders. Nat Rev Neurol. 2013;9:44–53.

CAS  PubMed  Google Scholar 

Grossniklaus HE, Geisert EE, Nickerson JM. Introduction to the retina. Prog mol biol transl sci. Elsevier B.V.; 2015. pp. 383–96.

McLaughlin T, Medina A, Perkins J, Yera M, Wang JJ, Zhang SX. Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications. Mol Neurodegener. 2022;17.

Martins B, Pires M, Ambrósio AF, Girão H, Fernandes R. Contribution of extracellular vesicles for the pathogenesis of retinal diseases: shedding light on blood-retinal barrier dysfunction. J Biomed Sci. 2024;31.

Bourne RRA, Steinmetz JD, Saylan M, Mersha AM, Weldemariam AH, Wondmeneh TG, et al. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the right to sight: an analysis for the global burden of disease study. Lancet Glob Health. 2021;9:e144–60.

Google Scholar 

Ptito M, Bleau M, Bouskila J. The retina: A window into the brain. Cells. 2021;10.

World Health Organization. World report on vision. Geneva; 2019.

Bourne RRA, Steinmetz JD, Flaxman S, Briant PS, Taylor HR, Resnikoff S, et al. Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the global burden of disease study. Lancet Glob Health. 2021;9:e130–43.

Google Scholar 

Balaggan KS, Ali RR. Ocular gene delivery using lentiviral vectors. Gene Ther. 2012;19:145–53.

CAS  PubMed  Google Scholar 

Zulliger R, Conley SM, Naash MI. Non-viral therapeutic approaches to ocular diseases: an overview and future directions. J Controlled Release. 2015;219:471–87.

CAS  Google Scholar 

Wang Y, Rajala A, Rajala R. Lipid nanoparticles for ocular gene delivery. J Funct Biomater. 2015;6:379–94.

CAS  PubMed  PubMed Central  Google Scholar 

Bennett J. History and development story of luxturna: scientific and regulatory challenges. In: McIntosh A, Sverdlov O, editors. Development of gene therapies. CRC Press - Taylor & Francis Group; 2024. pp. 407–24.

Brar AS, Parameswarappa DC, Takkar B, Narayanan R, Jalali S, Mandal S, et al. Gene therapy for inherited retinal diseases: from laboratory bench to patient bedside and beyond. Ophthalmol Ther. 2024;13:21–50.

PubMed  Google Scholar 

Bordet T, Behar-Cohen F. Ocular gene therapies in clinical practice: viral vectors and nonviral alternatives. Drug Discov Today. 2019;24:1685–93.

CAS  PubMed  Google Scholar 

Irigoyen C, Amenabar Alonso A, Sanchez-Molina J, Rodríguez-Hidalgo M, Lara-López A, Ruiz-Ederra J. Subretinal injection techniques for retinal disease: A review. J Clin Med. 2022;11.

Xue K, Groppe M, Salvetti AP, MacLaren RE. Technique of retinal gene therapy: delivery of viral vector into the subretinal space. Eye (Basingstoke). 2017;31:1308–16.

CAS  Google Scholar 

Devoldere J, Peynshaert K, Dewitte H, Vanhove C, De Groef L, Moons L, et al. Non-viral delivery of chemically modified mRNA to the retina: subretinal versus intravitreal administration. J Controlled Release. 2019;307:315–30.

CAS  Google Scholar 

Ross M, Ofri R. The future of retinal gene therapy: evolving from subretinal to intravitreal vector delivery. Neural Regen Res. 2021;16:1751–9.

CAS  PubMed  PubMed Central  Google Scholar 

Peynshaert K, Devoldere J, Minnaert AK, De Smedt SC, Remaut K. Morphology and composition of the inner limiting membrane: Species-Specific variations and relevance toward drug delivery research. Curr Eye Res. 2019;44:465–75.

CAS  PubMed  Google Scholar 

Jacob S, Nair AB, Shah J, Gupta S, Boddu SHS, Sreeharsha N et al. Lipid nanoparticles as a promising drug delivery carrier for topical ocular therapy; an overview on recent advances. Pharmaceutics. 2022;14.

Ryals RC, Patel S, Acosta C, McKinney M, Pennesi ME, Sahay G. The effects of pegylation on LNP based mRNA delivery to the eye. PLoS ONE. 2020;15.

Ramsay E, Lajunen T, Bhattacharya M, Reinisalo M, Rilla K, Kidron H, et al. Selective drug delivery to the retinal cells: biological barriers and avenues. J Controlled Release. 2023;361:1–19.

CAS  Google Scholar 

Dalkara D, Kolstad KD, Caporale N, Visel M, Klimczak RR, Schaffer DV, et al. Inner limiting membrane barriers to aav-mediated retinal transduction from the vitreous. Mol Ther. 2009;17:2096–102.

CAS  PubMed  PubMed Central  Google Scholar 

Johnson TV, Bull ND, Martin KR. Identification of barriers to retinal engraftment of transplanted stem cells. Invest Ophthalmol Vis Sci. 2010;51:960–70.

PubMed  PubMed Central  Google Scholar 

De Clerck K, De Smedt S, Remaut K, Peynshaert K. Toward successful retinal drug delivery after intravitreal injection: current strategies to overcome the inner limiting membrane. J Controlled Release. 2025;384:113849.

Google Scholar 

De Clerck K, Accou G, Sauvage F, Braeckmans K, De Smedt SC, Remaut K et al. Photodisruption of the inner limiting membrane: exploring ICG loaded nanoparticles as photosensitizers. Pharmaceutics. 2022;14.

Peynshaert K, Vanluchene H, De Clerck K, Minnaert AK, Verhoeven M, Gouspillou N, et al. ICG-mediated photodisruption of the inner limiting membrane enhances retinal drug delivery. J Controlled Release. 2022;349:315–26.

CAS  Google Scholar 

Peynshaert K, Devoldere J, De Smedt SC, Remaut K. In vitro and ex vivo models to study drug delivery barriers in the posterior segment of the eye. Adv Drug Deliv Rev. 2018;126:44–57.

CAS  PubMed  Google Scholar 

Peynshaert K, Devoldere J, Forster V, Picaud S, Vanhove C, De Smedt SC, et al. Toward smart design of retinal drug carriers: A novel bovine retinal explant model to study the barrier role of the vitreoretinal interface. Drug Deliv. 2017;24:1384–94.

CAS  PubMed  PubMed Central  Google Scholar 

Appell MB, Pejavar J, Pasupathy A, Rompicharla SVK, Abbasi S, Malmberg K, et al. Next generation therapeutics for retinal neurodegenerative diseases. J Controlled Release. 2024;367:708–36.

CAS  Google Scholar 

Tavakoli S, Peynshaert K, Lajunen T, Devoldere J, del Amo EM, Ruponen M, et al. Ocular barriers to retinal delivery of intravitreal liposomes: impact of vitreoretinal interface. J Controlled Release. 2020;328:952–61.

CAS  Google Scholar 

Bourges JL, Gautier SE, Delie F, Bejjani RA, Jeanny JC, Gurny R, et al. Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Invest Ophthalmol Vis Sci. 2003;44:3562–9.

PubMed  Google Scholar 

Peynshaert K, Devoldere J, De Smedt S, Remaut K. Every nano-step counts: a critical reflection on do’s and don’ts in researching nanomedicines for retinal gene therapy. Expert Opin Drug Deliv. 2023;20:259–71.

PubMed  Google Scholar 

Meulewaeter S, Aernout I, Deprez J, Engelen Y, De Velder M, Franceschini L, et al. Alpha-galactosylceramide improves the potency of mRNA LNP vaccines against cancer and intracellular bacteria. J Controlled Release. 2024;370:379–91.

CAS  Google Scholar 

Reinhart A-G, Osterwald A, Ringler P, Leiser Y, Lauer ME, Martin RE, et al. Investigations into mRNA lipid nanoparticles Shelf-Life stability under nonfrozen conditions. Mol Pharm. 2023;20:6492–503.

CAS  PubMed  Google Scholar 

Limb GA, Salt TE, Munro PMG, Moss SE, Khaw PT. In vitro characterization of a spontaneously immortalized human Müller cell line (MIO-M1). Retinal Cell Biology. 2002;43.

Martens TF, Vercauteren D, Forier K, Deschout H, Remaut K, Paesen R, et al. Measuring the intravitreal mobility of nanomedicines with Single-Particle tracking microscopy. Nanomedicine. 2013;8:1955–68.

CAS  PubMed  Google Scholar 

Subramanya S, Fernando R, Goswami M, Besirli CG, Weh E, Wubben TJ. Flow cytometric method for the detection and quantification of retinal cell death and oxidative stress. Exp Eye Res. 2023;233.

Chang ZY, Lu DW, Yeh MK, Chiang CH. A novel high-content flow cytometric method for assessing the viability and damage of rat retinal ganglion cells. PLoS ONE. 2012;7.

Brunet AA, Fuller-Carter PI, Miller AL, Voigt V, Vasiliou S, Rashwan R, et al. Validating fluorescent chrnb4.Egfp mouse models for the study of cone photoreceptor degeneration. Transl Vis Sci Technol. 2020;9:1–13.

Google Scholar 

Lukowski SW, Lo CY, Sharov AA, Nguyen Q, Fang L, Hung SS et al. A single-cell transcriptome atlas of the adult human retina. EMBO J. 2019;38.

Liu B, He J, Zhong L, Huang L, Gong B, Hu J et al. Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula. Front Neurosci. 2022;16.

Bakken TE, Hodge RD, Miller JA, Yao Z, Nguyen TN, Aevermann B et al. Single-nucleus and single-cell transcriptomes compared in matched cortical cell types. PLoS ONE. 2018;13.

Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell. 2015;161:1202–14.

CAS  PubMed  PubMed Central  Google Scholar 

Garafalo AV, Cideciyan AV, Héon E, Sheplock R, Pearson A, WeiYang Yu C et al. Progress in treating inherited retinal diseases: early subretinal gene therapy clinical trials and candidates for future initiatives. Prog Retin Eye Res. 2020;77.

Gautam M, Jozic A, Su GL-N, Herrera-Barrera M, Curtis A, Arrizabalaga S, et al. Lipid nanoparticles with PEG-variant surface modifications mediate genome editing in the mouse retina. Nat Commun. 2023;14:6468.

CAS  PubMed  PubMed Central  Google Scholar 

Kim J, Eygeris Y, Ryals RC, Jozić A, Sahay G. Strategies for non-viral vectors targeting organs beyond the liver. Nat Nanotechnol. 2024;19:428–47.

CAS  PubMed  Google Scholar 

Xu Q, Boylan NJ, Suk JS, Wang Y-Y, Nance EA, Yang J-C, et al. Nanoparticle diffusion in, and microrheology of, the bovine vitreous ex vivo. J Controlled Release. 2013;167:76–84.

CAS  Google Scholar 

Pitkanen L, Pelkonen J, Ruponen M, Ronkko S, Urtti A. Neural retina limits the Non viral gene transfer to retinal pigment epithelium in an in vitro bovine eye model. AAPS J. 2004;6.

Koo H, Moon H, Han H, Na JH, Huh MS, Park JH, et al. The movement of self-assembled amphiphilic polymeric nanoparticles in the vitreous and retina after intravitreal injection. Biomaterials. 2012;33:3485–93.

CAS  PubMed  Google Scholar 

Peynshaert K, Fradot V, Picaud S, De Smedt S, Remaut K. Toward rational design of gene carriers: a novel ex vivo model to study the vitreoretinal interface as a barrier. Acta Ophthalmol. 2016;94.

Devoldere J, Wels M, Peynshaert K, Dewitte H, De Smedt SC, Remaut K. The obstacle course to the inner retina: hyaluronic acid-coated lipoplexes cross the vitreous but fail to overcome the inner limiting membrane. Eur J Pharm Biopharm. 2019;141:161–71.

CAS  PubMed  Google Scholar 

Heegaard S, Jensen OA, Prause JU. Structure and composition of the inner limiting membrane of the retina. SEM on frozen resin-cracked and enzyme-digested retinas of Macacca mulatta. Graefe’s Arch Clin Exp Ophthalmol. 1986;224:355–60.

CAS  Google Scholar 

Zhang KY, Tuffy C, Mertz JL, Quillen S, Wechsler L, Quigley HA, et al. Role of the internal limiting membrane in structural engraftment and topographic spacing of transplanted human stem Cell-Derived retinal ganglion cells. Stem Cell Rep. 2021;16:149–67.