{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:37:42Z","timestamp":1790721462793,"version":"4.1.0"},"reference-count":161,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01EY029339"],"award-info":[{"award-number":["R01EY029339"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["K12 EY021475"],"award-info":[{"award-number":["K12 EY021475"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NEI","doi-asserted-by":"publisher","award":["R01EY029339"],"award-info":[{"award-number":["R01EY029339"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NEI","doi-asserted-by":"publisher","award":["K12 EY021475"],"award-info":[{"award-number":["K12 EY021475"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cell-penetrating peptides (CPPs) are short peptides with the ability to translocate through the cell membrane to facilitate their cellular uptake. CPPs can be used as drug-delivery systems for molecules that are difficult to uptake. Ocular drug delivery is challenging due to the structural and physiological complexity of the eye. CPPs may be tailored to overcome this challenge, facilitating cellular uptake and delivery to the targeted area. Retinal diseases occur at the posterior pole of the eye; thus, intravitreal injections are needed to deliver drugs at an effective concentration in situ. However, frequent injections have risks of causing vision-threatening complications. Recent investigations have focused on developing long-acting drugs and drug delivery systems to reduce the frequency of injections. In fact, conjugation with CPP could deliver FDA-approved drugs to the back of the eye, as seen by topical application in animal models. This review summarizes recent advances in CPPs, protein\/peptide-based drugs for eye diseases, and the use of CPPs for drug delivery based on systematic searches in PubMed and clinical trials. We highlight targeted therapies and explore the potential of CPPs and peptide-based drugs for eye diseases.<\/jats:p>","DOI":"10.3390\/cells12071071","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T01:37:05Z","timestamp":1680485825000},"page":"1071","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Ocular Delivery of Therapeutic Agents by Cell-Penetrating Peptides"],"prefix":"10.3390","volume":"12","author":[{"given":"Nguy\u1ec5n Th\u1ecb Thanh","family":"Nh\u00e0n","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3447-4074","authenticated-orcid":false,"given":"Daniel E.","family":"Maidana","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, Chicago, IL 60612, USA"},{"name":"Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-9866","authenticated-orcid":false,"given":"Kaori H.","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"},{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,1]]},"reference":[{"key":"ref_1","unstructured":"(2019). World Report on Vision. Licence: CC BY-NC-SA 3.0 IGO, World Health Organization."},{"key":"ref_2","unstructured":"(2022). Common Eye Disorders and Diseases."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1208\/s12248-010-9183-3","article-title":"Ocular drug delivery","volume":"12","author":"Gaudana","year":"2010","journal-title":"AAPS J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.2147\/DDDT.S94188","article-title":"Profile of adalimumab and its potential in the treatment of uveitis","volume":"10","author":"Balevic","year":"2016","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18088","DOI":"10.1038\/s41598-017-18412-9","article-title":"Intravitreal injections of anti-VEGF agents and antibiotic prophylaxis for endophthalmitis: A systematic review and meta-analysis","volume":"7","author":"Bande","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.3928\/15428877-20120517-03","article-title":"Successful management of choroidal metastasis with intravitreal ranibizumab injections","volume":"43","author":"Detorakis","year":"2012","journal-title":"Ophthalmic Surg. Lasers Imaging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/eye.2009.94","article-title":"Therapeutic effect of bevacizumab injected into the silicone oil in eyes with neovascular glaucoma after vitrectomy for advanced diabetic retinopathy","volume":"24","author":"Falavarjani","year":"2010","journal-title":"Eye"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1007\/s00417-010-1315-z","article-title":"A review of clinical trials of anti-VEGF agents for diabetic retinopathy","volume":"248","author":"Nicholson","year":"2010","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0140-6736(07)61104-0","article-title":"Clinical update: New treatments for age-related macular degeneration","volume":"370","author":"Wong","year":"2007","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100125","DOI":"10.1016\/j.crmeth.2021.100125","article-title":"An intravitreal implant injection method for sustained drug delivery into mouse eyes","volume":"1","author":"Sun","year":"2021","journal-title":"Cell Rep. Methods"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4749","DOI":"10.1167\/iovs.10-6291","article-title":"Pharmacokinetics of pars plana intravitreal injections versus microcannula suprachoroidal injections of bevacizumab in a porcine model","volume":"52","author":"Olsen","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.ajo.2006.05.045","article-title":"Cannulation of the suprachoroidal space: A novel drug delivery methodology to the posterior segment","volume":"142","author":"Olsen","year":"2006","journal-title":"Am. J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1097\/IAE.0b013e3182278b0e","article-title":"Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudates","volume":"32","author":"Rizzo","year":"2012","journal-title":"Retina"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/17425247.2016.1218460","article-title":"Minimally invasive microneedles for ocular drug delivery","volume":"14","author":"Tekko","year":"2017","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"116907","DOI":"10.1016\/j.lfs.2019.116907","article-title":"Applications of microneedles in delivering drugs for various ocular diseases","volume":"237","author":"Gupta","year":"2019","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/j.1444-0938.2010.00553.x","article-title":"Drug delivery to the posterior segment of the eye through hydrogel contact lenses","volume":"94","author":"Schultz","year":"2011","journal-title":"Clin. Exp. Optom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.1167\/iovs.08-3148","article-title":"Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits","volume":"50","author":"Nomoto","year":"2009","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/08820530902802013","article-title":"The Boston Ocular Surface Prosthesis as a novel drug delivery system for bevacizumab","volume":"24","author":"Lim","year":"2009","journal-title":"Semin. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"119285","DOI":"10.1016\/j.biomaterials.2019.119285","article-title":"Topical sustained drug delivery to the retina with a drug-eluting contact lens","volume":"217","author":"Ross","year":"2019","journal-title":"Biomaterials"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"309ra165","DOI":"10.1126\/scitranslmed.aac4882","article-title":"The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease","volume":"7","author":"Sidman","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.ophtha.2017.03.057","article-title":"Brolucizumab Versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized Trial","volume":"124","author":"Dugel","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ophtha.2019.04.017","article-title":"HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration","volume":"127","author":"Dugel","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.ophtha.2020.11.011","article-title":"Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER","volume":"128","author":"Mones","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1001\/jamaophthalmol.2020.5053","article-title":"Efficacy and Safety of a Proposed Ranibizumab Biosimilar Product vs a Reference Ranibizumab Product for Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial","volume":"139","author":"Woo","year":"2021","journal-title":"JAMA Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1136\/bjophthalmol-2021-319637","article-title":"Biosimilar SB11 versus reference ranibizumab in neovascular age-related macular degeneration: 1-year phase III randomised clinical trial outcomes","volume":"107","author":"Bressler","year":"2021","journal-title":"Br. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.molmed.2022.03.004","article-title":"Viewpoints: Dual-blocking antibody against VEGF-A and angiopoietin-2 for treating vascular diseases of the eye","volume":"28","author":"Koh","year":"2022","journal-title":"Trends Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0140-6736(22)00018-6","article-title":"Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): Two randomised, double-masked, phase 3 trials","volume":"399","author":"Wykoff","year":"2022","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0140-6736(22)00010-1","article-title":"Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): Two randomised, double-masked, phase 3, non-inferiority trials","volume":"399","author":"Heier","year":"2022","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ophtha.2021.09.016","article-title":"Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration","volume":"129","author":"Holekamp","year":"2022","journal-title":"Ophthalmology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1056\/NEJMoa054481","article-title":"Ranibizumab for neovascular age-related macular degeneration","volume":"355","author":"Rosenfeld","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ajo.2007.10.004","article-title":"Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1","volume":"145","author":"Regillo","year":"2008","journal-title":"Am. J. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ophtha.2008.10.018","article-title":"Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study","volume":"116","author":"Brown","year":"2009","journal-title":"Ophthalmology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1517\/13543780903201684","article-title":"VEGF Trap-Eye for the treatment of neovascular age-related macular degeneration","volume":"18","author":"Dixon","year":"2009","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_34","unstructured":"(2023, February 21). Eylea\u00ae (Aflibercept) Injection Approved as the First Pharmacologic Treatment for Preterm Infants with Retinopathy of Prematurity (ROP) by the FDA. Available online: https:\/\/investor.regeneron.com\/news-releases\/news-release-details\/eylear-aflibercept-injection-approved-first-pharmacologic."},{"key":"ref_35","first-page":"348","article-title":"Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity: The FIREFLEYE Randomized Clinical Trial","volume":"328","author":"Stahl","year":"2022","journal-title":"JAMA Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1167\/iovs.16-20072","article-title":"Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides","volume":"58","author":"Hill","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1476-5381.2009.00057.x","article-title":"Twenty years of cell-penetrating peptides: From molecular mechanisms to therapeutics","volume":"157","author":"Heitz","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Borrelli, A., Tornesello, A.L., Tornesello, M.L., and Buonaguro, F.M. (2018). Cell Penetrating Peptides as Molecular Carriers for Anti-Cancer Agents. Molecules, 23.","DOI":"10.3390\/molecules23020295"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.tips.2017.01.003","article-title":"Cell-Penetrating Peptides: From Basic Research to Clinics","volume":"38","author":"Guidotti","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1080\/02713683.2020.1830117","article-title":"Stability of Cell-Penetrating Peptide anti-VEGF Formulations for the Treatment of Age-Related Macular Degeneration","volume":"46","author":"Nikoi","year":"2021","journal-title":"Curr. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/0092-8674(88)90263-2","article-title":"Cellular uptake of the tat protein from human immunodeficiency virus","volume":"55","author":"Frankel","year":"1988","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10444","DOI":"10.1016\/S0021-9258(17)34080-2","article-title":"The third helix of the Antennapedia homeodomain translocates through biological membranes","volume":"269","author":"Derossi","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1006\/excr.2001.5316","article-title":"VE-cadherin-derived cell-penetrating peptide, pVEC, with carrier functions","volume":"269","author":"Elmquist","year":"2001","journal-title":"Exp. Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1021\/acs.accounts.6b00074","article-title":"How Membrane-Active Peptides Get into Lipid Membranes","volume":"49","author":"Sani","year":"2016","journal-title":"Acc. Chem. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1021\/nn4057269","article-title":"Cell-penetrating peptides: Design, synthesis, and applications","volume":"8","author":"Copolovici","year":"2014","journal-title":"ACS Nano"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/0092-8674(88)90262-0","article-title":"Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein","volume":"55","author":"Green","year":"1988","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/ncomms1459","article-title":"Backbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides","volume":"2","author":"Prinz","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1016\/j.bbamem.2015.09.004","article-title":"Protein transport across membranes: Comparison between lysine and guanidinium-rich carriers","volume":"1848","author":"Lein","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13003","DOI":"10.1073\/pnas.97.24.13003","article-title":"The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters","volume":"97","author":"Wender","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9506","DOI":"10.1021\/ja0482536","article-title":"Role of membrane potential and hydrogen bonding in the mechanism of translocation of guanidinium-rich peptides into cells","volume":"126","author":"Rothbard","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/j.bbamem.2007.03.004","article-title":"Counterion-mediated membrane penetration: Cationic cell-penetrating peptides overcome Born energy barrier by ion-pairing with phospholipids","volume":"1768","author":"Esbjorner","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/psc.968","article-title":"Live-cell analysis of cell penetration ability and toxicity of oligo-arginines","volume":"14","author":"Tunnemann","year":"2008","journal-title":"J. Pept. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/nm996","article-title":"Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis","volume":"10","author":"Wadia","year":"2004","journal-title":"Nat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.bpj.2010.03.065","article-title":"Cell-penetrating HIV1 TAT peptides can generate pores in model membranes","volume":"99","author":"Ciobanasu","year":"2010","journal-title":"Biophys. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17459","DOI":"10.1021\/ja507790z","article-title":"Fundamental molecular mechanism for the cellular uptake of guanidinium-rich molecules","volume":"136","author":"Herce","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"20785","DOI":"10.1039\/C4CP02211D","article-title":"Effect of arginine-rich cell penetrating peptides on membrane pore formation and life-times: A molecular simulation study","volume":"16","author":"Sun","year":"2014","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"11923","DOI":"10.1073\/pnas.1811520115","article-title":"Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore","volume":"115","author":"Allolio","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajo.2016.10.012","article-title":"Postoperative Ocular Inflammation: A Single Subconjunctival Injection of XG-102 Compared to Dexamethasone Drops in a Randomized Trial","volume":"174","author":"Chiquet","year":"2017","journal-title":"Am. J. Ophthalmol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1097\/MAO.0000000000002229","article-title":"Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness-A Double-blind, Randomized, Placebo-controlled Phase 3 Study","volume":"40","author":"Staecker","year":"2019","journal-title":"Otol. NeurOtol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jconrel.2014.05.056","article-title":"Low molecular weight protamine (LMWP): A nontoxic protamine substitute and an effective cell-penetrating peptide","volume":"193","author":"He","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7733","DOI":"10.1016\/j.biomaterials.2013.06.047","article-title":"The use of low molecular weight protamine chemical chimera to enhance monomeric insulin intestinal absorption","volume":"34","author":"He","year":"2013","journal-title":"Biomaterials"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.bbrc.2017.05.148","article-title":"Control of cancer stem cell like population by intracellular target identification followed by the treatment with peptide-siRNA complex","volume":"491","author":"Suh","year":"2017","journal-title":"BioChem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1021\/bc300520t","article-title":"Activatable cell penetrating peptide-conjugated nanoparticles with enhanced permeability for site-specific targeting delivery of anticancer drug","volume":"24","author":"Xia","year":"2013","journal-title":"Bioconjug. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jconrel.2014.06.051","article-title":"Low-molecular-weight protamine-modified PLGA nanoparticles for overcoming drug-resistant breast cancer","volume":"192","author":"Wang","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9888","DOI":"10.1016\/j.biomaterials.2011.09.004","article-title":"Low molecular weight protamine-functionalized nanoparticles for drug delivery to the brain after intranasal administration","volume":"32","author":"Xia","year":"2011","journal-title":"Biomaterials"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.drudis.2012.03.002","article-title":"Cell-penetrating peptides: Classes, origin, and current landscape","volume":"17","author":"Milletti","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Kalafatovic, D., and Giralt, E. (2017). Cell-Penetrating Peptides: Design Strategies beyond Primary Structure and Amphipathicity. Molecules, 22.","DOI":"10.3390\/molecules22111929"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1042\/BC20070116","article-title":"Cell-penetrating peptides: From molecular mechanisms to therapeutics","volume":"100","author":"Morris","year":"2008","journal-title":"Biol. Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0005-2736(98)00161-8","article-title":"Cellular uptake of an alpha-helical amphipathic model peptide with the potential to deliver polar compounds into the cell interior non-endocytically","volume":"1414","author":"Oehlke","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/nbt0998-857","article-title":"Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo","volume":"16","author":"Pooga","year":"1998","journal-title":"Nat. Biotechnol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"14150","DOI":"10.1021\/bi026661l","article-title":"Translocating proline-rich peptides from the antimicrobial peptide bactenecin 7","volume":"41","author":"Sadler","year":"2002","journal-title":"Biochemistry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.addr.2007.09.012","article-title":"Proline-rich, amphipathic cell-penetrating peptides","volume":"60","author":"Pujals","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/bip.10585","article-title":"Amphipathic peptides and drug delivery","volume":"76","author":"Kogan","year":"2004","journal-title":"Biopolymers"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.1021\/acs.jpcb.0c01618","article-title":"Prediction of Amphiphilic Cell-Penetrating Peptide Building Blocks from Protein-Derived Amino Acid Sequences for Engineering of Drug Delivery Nanoassemblies","volume":"124","author":"Feger","year":"2020","journal-title":"J. Phys. Chem. B"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4906","DOI":"10.1038\/s41467-019-12922-y","article-title":"Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia","volume":"10","author":"Krishnamurthy","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1074\/jbc.M509813200","article-title":"Mechanism of uptake of C105Y, a novel cell-penetrating peptide","volume":"281","author":"Rhee","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8995","DOI":"10.1021\/ja2017416","article-title":"Spontaneous membrane-translocating peptides by orthogonal high-throughput screening","volume":"133","author":"Marks","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7328","DOI":"10.1002\/anie.201502358","article-title":"Ring Tension Applied to Thiol-Mediated Cellular Uptake","volume":"54","author":"Gasparini","year":"2015","journal-title":"Angew Chem. Int. Ed. Engl."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1096\/fj.08-127563","article-title":"Cell-surface thiols affect cell entry of disulfide-conjugated peptides","volume":"23","author":"Aubry","year":"2009","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/s41557-021-00661-x","article-title":"Cellular uptake of large biomolecules enabled by cell-surface-reactive cell-penetrating peptide additives","volume":"13","author":"Schneider","year":"2021","journal-title":"Nat. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7923","DOI":"10.1039\/C7SC03918B","article-title":"Peptide\/Cas9 nanostructures for ribonucleoprotein cell membrane transport and gene edition","volume":"8","author":"Louzao","year":"2017","journal-title":"Chem. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/cbic.200900527","article-title":"Delivery of macromolecules into live cells by simple co-incubation with a peptide","volume":"11","author":"Lee","year":"2010","journal-title":"Chembiochem"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.bbamem.2006.02.021","article-title":"Peptide-membrane interactions and mechanisms of membrane destruction by amphipathic alpha-helical antimicrobial peptides","volume":"1758","author":"Sato","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nchembio.2153","article-title":"Biophysical determinants for cellular uptake of hydrocarbon-stapled peptide helices","volume":"12","author":"Bird","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1021\/mp200481g","article-title":"Comparison of cationic and amphipathic cell penetrating peptides for siRNA delivery and efficacy","volume":"9","author":"Mo","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1124\/jpet.119.256933","article-title":"Ocular Drug Delivery: Present Innovations and Future Challenges","volume":"370","author":"Gote","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jconrel.2018.06.023","article-title":"Cell penetrating peptides in ocular drug delivery: State of the art","volume":"284","author":"Pescina","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1038\/s41433-022-02153-9","article-title":"15 years of anti-VEGF treatment for nAMD: Success or failure or something in between?","volume":"36","author":"Chakravarthy","year":"2022","journal-title":"Eye"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Bohni, S.C., Bittner, M., Howell, J.P., Bachmann, L.M., Faes, L., and Schmid, M.K. (2015). Comparison of Eylea(R) with Lucentis(R) as first-line therapy in patients with treatment-naive neovascular age-related macular degeneration in real-life clinical practice: Retrospective case-series analysis. BMC Ophthalmol., 15.","DOI":"10.1186\/s12886-015-0101-4"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.survophthal.2012.01.007","article-title":"Corneal neovascularization: An anti-VEGF therapy review","volume":"57","author":"Chang","year":"2012","journal-title":"Surv. Ophthalmol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/nm1010-1107","article-title":"Vascular endothelial growth factor and age-related macular degeneration: From basic science to therapy","volume":"16","author":"Ferrara","year":"2010","journal-title":"Nat. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"11393","DOI":"10.1073\/pnas.172398299","article-title":"VEGF-Trap: A VEGF blocker with potent antitumor effects","volume":"99","author":"Holash","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/nrd1381","article-title":"Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer","volume":"3","author":"Ferrara","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc1913","article-title":"Comparing antibody and small-molecule therapies for cancer","volume":"6","author":"Imai","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/s41551-021-00698-w","article-title":"The evolution of commercial drug delivery technologies","volume":"5","author":"Vargason","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/cbdd.12055","article-title":"The future of peptide-based drugs","volume":"81","author":"Craik","year":"2013","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.4155\/tde.13.104","article-title":"Basics and recent advances in peptide and protein drug delivery","volume":"4","author":"Bruno","year":"2013","journal-title":"Ther. Deliv."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1016\/j.bmc.2017.06.052","article-title":"Therapeutic peptides: Historical perspectives, current development trends, and future directions","volume":"26","author":"Lau","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41392-022-00904-4","article-title":"Therapeutic peptides: Current applications and future directions","volume":"7","author":"Wang","year":"2022","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide therapeutics: Current status and future directions","volume":"20","author":"Fosgerau","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1208\/s12248-014-9687-3","article-title":"Strategic approaches to optimizing peptide ADME properties","volume":"17","author":"Di","year":"2015","journal-title":"AAPS J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.4103\/1673-5374.332147","article-title":"A novel approach in preventing vascular leakage and angiogenesis in wet age-related macular degeneration","volume":"17","author":"Yamada","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Yoon, C.K., Oh, J., Bae, K., Park, U.C., Yu, K.S., and Yu, H.G. (2022). Efficacy and safety of a new ranibizumab biosimilar CKD-701 using a pro re nata treatment regimen in neovascular age-related macular degeneration: A phase 3 randomized clinical trial. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0275611"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.18240\/ijo.2022.09.20","article-title":"Efficacy and safety of intravitreal HLX04-O, an anti-VEGF monoclonal antibody, for the treatment of wet age-related macular degeneration","volume":"15","author":"Zhang","year":"2022","journal-title":"Int. J. Ophthalmol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1016\/j.ophtha.2014.03.026","article-title":"Safety and efficacy of conbercept in neovascular age-related macular degeneration: Results from a 12-month randomized phase 2 study: AURORA study","volume":"121","author":"Li","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.ajo.2018.08.026","article-title":"Conbercept for Treatment of Neovascular Age-related Macular Degeneration: Results of the Randomized Phase 3 PHOENIX Study","volume":"197","author":"Liu","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1097\/IAE.0000000000001404","article-title":"Efficacy and Safety of Intravitreal Conbercept Injections in Macular Edema Secondary to Retinal Vein Occlusion","volume":"37","author":"Sun","year":"2017","journal-title":"Retina"},{"key":"ref_108","first-page":"CD009510","article-title":"Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion","volume":"7","author":"Shalchi","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_109","first-page":"382-F0213","article-title":"Efficacy and Safety of OPT-302 in combination with Ranibizumab for Polypoidal Choroidal Vasculopathy","volume":"63","author":"Slakter","year":"2022","journal-title":"IOVS"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Jackson, T.L., Slakter, J., Buyse, M., Wang, K., Dugel, P.U., Wykoff, C.C., Boyer, D.S., Gerometta, M., Baldwin, M.E., and Price, C.F. (2023). A randomized controlled trial of OPT-302, a VEGF-C\/D inhibitor for neovascular age-related macular degeneration. Ophthalmology, in press.","DOI":"10.1016\/j.ophtha.2023.02.001"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.ophtha.2020.03.035","article-title":"Efficacy and Safety of Abicipar in Neovascular Age-Related Macular Degeneration: 52-Week Results of Phase 3 Randomized Controlled Study","volume":"127","author":"Kunimoto","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_112","first-page":"1655","article-title":"Phase I Mp0112 Wet AMD Study: Results Of A Single Escalating Dose Study With DARPin\u00ae MP0112 In Wet AMD","volume":"52","author":"Wolf","year":"2011","journal-title":"IOVS"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1097\/IAE.0000000000003441","article-title":"Intravitreal Nesvacumab (Antiangiopoietin 2) Plus Aflibercept in Diabetic Macular Edema: Phase 2 RUBY Randomized Trial","volume":"42","author":"Brown","year":"2022","journal-title":"Retina"},{"key":"ref_114","unstructured":"(2023, February 09). AffaMed Therapeutics Announces First Patient Dosed in the US Phase 1 Clinical Trial of AM712 in Retinal Disease. Available online: https:\/\/www.affamed.com\/press-releases-37."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3928\/23258160-20170130-02","article-title":"An Overview of the Fovista and Rinucumab Trials and the Fate of Anti-PDGF Medications","volume":"48","author":"Dunn","year":"2017","journal-title":"Ophthalmic Surg. Lasers Imaging Retin."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.ophtha.2016.10.010","article-title":"Dual Antagonism of PDGF and VEGF in Neovascular Age-Related Macular Degeneration: A Phase IIb, Multicenter, Randomized Controlled Trial","volume":"124","author":"Jaffe","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"9945725","DOI":"10.1155\/2021\/9945725","article-title":"Complement Inhibitors in Age-Related Macular Degeneration: A Potential Therapeutic Option","volume":"2021","author":"Qin","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1001\/jamaophthalmol.2018.1544","article-title":"Efficacy and Safety of Lampalizumab for Geographic Atrophy Due to Age-Related Macular Degeneration: Chroma and Spectri Phase 3 Randomized Clinical Trials","volume":"136","author":"Holz","year":"2018","journal-title":"JAMA Ophthalmol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.ophtha.2013.09.044","article-title":"Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: The COMPLETE study","volume":"121","author":"Yehoshua","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"100154","DOI":"10.1016\/j.xops.2022.100154","article-title":"A Phase I, Single Ascending Dose Study of GEM103 (Recombinant Human Complement Factor H) in Patients with Geographic Atrophy","volume":"2","author":"Khanani","year":"2022","journal-title":"Ophthalmol. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Lashkari, K., Teague, G., Chen, H., Lin, Y.Q., Kumar, S., McLaughlin, M.M., and Lopez, F.J. (2018). A monoclonal antibody targeting amyloid beta (Abeta) restores complement factor I bioactivity: Potential implications in age-related macular degeneration and Alzheimer\u2019s disease. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195751"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1136\/bjophthalmol-2020-318452","article-title":"Treatments for dry age-related macular degeneration: Therapeutic avenues, clinical trials and future directions","volume":"106","author":"Georgiou","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.oret.2018.03.001","article-title":"A Randomized Phase 2 Study of an Anti-Amyloid beta Monoclonal Antibody in Geographic Atrophy Secondary to Age-Related Macular Degeneration","volume":"2","author":"Rosenfeld","year":"2018","journal-title":"Ophthalmol. Retin."},{"key":"ref_124","first-page":"24","article-title":"New Pathways for Dry AMD Treatment several potential therapies are in clinical trials","volume":"16","author":"David","year":"2019","journal-title":"Retin. Physician"},{"key":"ref_125","unstructured":"(2023, February 07). Apellis Completes Enrollment in Two Phase 3 Studies of the Targeted C3 Therapy, Pegcetacoplan, in Patients with Geographic Atrophy (GA). Available online: https:\/\/investors.apellis.com\/news-releases\/news-release-details\/apellis-completes-enrollment-two-phase-3-studies-targeted-c3."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"eabj2177","DOI":"10.1126\/scitranslmed.abj2177","article-title":"Targeting C3b\/C4b and VEGF with a bispecific fusion protein optimized for neovascular age-related macular degeneration therapy","volume":"14","author":"Yang","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ajo.2022.11.016","article-title":"A Novel Bispecific Fusion Protein Targeting C3b\/C4b and VEGF in Patients With nAMD: A Randomized, Open-Label, Phase 1b Study","volume":"248","author":"Jia","year":"2022","journal-title":"Am. J. Ophthalmol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1111\/bph.15459","article-title":"Emerging therapies and their delivery for treating age-related macular degeneration","volume":"179","author":"Thomas","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1167\/tvst.10.14.27","article-title":"Safety and Tolerability of Intravitreal Carotuximab (DE-122) in Patients With Persistent Exudative Age-Related Macular Degeneration: A Phase I Study","volume":"10","author":"Gonzalez","year":"2021","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_130","unstructured":"(2023, February 07). Lpath\u2019s iSONEP Fails in Phase II Wet-AMD Study. Available online: https:\/\/www.thepharmaletter.com\/article\/lpath-s-isonep-fails-in-phase-ii-wet-amd-study."},{"key":"ref_131","unstructured":"(2023, February 09). Late-Onset Retinal Degeneration Clinical Trials. Available online: https:\/\/www.medifind.com\/conditions\/late-onset-retinal-degeneration\/4620\/clinical-trial\/6047940."},{"key":"ref_132","first-page":"450","article-title":"Multicenter Phase 1 Clinical Trial Targeting Tissue Factor for the Treatment of Neovascular AMD","volume":"53","author":"Wells","year":"2012","journal-title":"IOVS"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1038\/s41433-021-01766-w","article-title":"An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma","volume":"36","author":"Ghanchi","year":"2022","journal-title":"Eye"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1097\/ICO.0000000000000627","article-title":"Dry Eye Signs and Symptoms Persist During Systemic Neutralization of IL-1beta by Canakinumab or IL-17A by Secukinumab","volume":"34","author":"Grosskreutz","year":"2015","journal-title":"Cornea"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1007\/s40123-022-00488-w","article-title":"An Introduction to Biosimilars for the Treatment of Retinal Diseases: A Narrative Review","volume":"11","author":"Hariprasad","year":"2022","journal-title":"Ophthalmol. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40942-021-00343-3","article-title":"Future of anti-VEGF: Biosimilars and biobetters","volume":"8","author":"Kapur","year":"2022","journal-title":"Int. J. Retin. Vitr."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1097\/IAE.0000000000003236","article-title":"Retinal Microvascular Changes in Uveal Melanoma Following Conbercept Injection after Plaque Radiotherapy as Detected by Optical Coherence Tomography Angiography","volume":"41","author":"Yang","year":"2021","journal-title":"Retina"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/s41433-019-0584-y","article-title":"Abicipar pegol-a novel anti-VEGF therapy with a long duration of action","volume":"34","author":"Moisseiev","year":"2020","journal-title":"Eye"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.1167\/iovs.18-25307","article-title":"Functional Characterization of Abicipar-Pegol, an Anti-VEGF DARPin Therapeutic That Potently Inhibits Angiogenesis and Vascular Permeability","volume":"59","author":"Rodrigues","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_140","unstructured":"Holekamp, N.M. (2023, February 07). Abicipar Pegol not Approved for Treatment of Wet AMD\u2014Healio. Available online: https:\/\/www.healio.com\/news\/ophthalmology\/20200626\/abicipar-pegol-not-approved-for-treatment-of-wet-amd."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1158\/1078-0432.CCR-15-1221","article-title":"A Phase I First-in-Human Study of Nesvacumab (REGN910), a Fully Human Anti-Angiopoietin-2 (Ang2) Monoclonal Antibody, in Patients with Advanced Solid Tumors","volume":"22","author":"Papadopoulos","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1016\/j.ophtha.2013.05.018","article-title":"A 4-year longitudinal study of 555 patients treated with ranibizumab for neovascular age-related macular degeneration","volume":"120","author":"Rasmussen","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_143","first-page":"1849","article-title":"Real-world variability in ranibizumab treatment and associated clinical, quality of life, and safety outcomes over 24 months in patients with neovascular age-related macular degeneration: The HELIOS study","volume":"7","author":"Rakic","year":"2013","journal-title":"Clin. Ophthalmol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1136\/bjophthalmol-2014-305327","article-title":"Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration","volume":"99","author":"Holz","year":"2015","journal-title":"Br. J. Ophthalmol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"157","DOI":"10.18240\/ijo.2022.01.23","article-title":"Progress of clinical therapies for dry age-related macular degeneration","volume":"15","author":"Rubner","year":"2022","journal-title":"Int. J. Ophthalmol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/sj.eye.6702176","article-title":"The complement system and age-related macular degeneration","volume":"20","author":"Sivaprasad","year":"2006","journal-title":"Eye"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1007\/s40265-021-01560-8","article-title":"Pegcetacoplan: First Approval","volume":"81","author":"Hoy","year":"2021","journal-title":"Drugs"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.exer.2016.02.004","article-title":"IBI302, a promising candidate for AMD treatment, targeting both the VEGF and complement system with high binding affinity in vitro and effective targeting of the ocular tissue in healthy rhesus monkeys","volume":"145","author":"Ren","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1167\/tvst.9.9.7","article-title":"DS-7080a, a Selective Anti-ROBO4 Antibody, Shows Anti-Angiogenic Efficacy with Distinctly Different Profiles from Anti-VEGF Agents","volume":"9","author":"Isumi","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1080\/13543784.2020.1763953","article-title":"Risuteganib-a novel integrin inhibitor for the treatment of non-exudative (dry) age-related macular degeneration and diabetic macular edema","volume":"29","author":"Shaw","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2337\/diabetes.50.1.77","article-title":"Cell-permeable peptide inhibitors of JNK: Novel blockers of beta-cell death","volume":"50","author":"Bonny","year":"2001","journal-title":"Diabetes"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1007\/s10792-020-01391-8","article-title":"Sustained subconjunctival drug delivery systems: Current trends and future perspectives","volume":"40","author":"Rafiei","year":"2020","journal-title":"Int. Ophthalmol."},{"key":"ref_153","first-page":"4518","article-title":"KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of VEGFR2","volume":"127","author":"Yamada","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ajpath.2016.09.010","article-title":"Antiangiogenic Therapeutic Potential of Peptides Derived from the Molecular Motor KIF13B that Transports VEGFR2 to Plasmalemma in Endothelial Cells","volume":"187","author":"Yamada","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1167\/iovs.62.2.5","article-title":"VEGFR2 Trafficking by KIF13B Is a Novel Therapeutic Target for Wet Age-Related Macular Degeneration","volume":"62","author":"Waters","year":"2021","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/sj.mt.6300324","article-title":"Cell-penetrating peptide for enhanced delivery of nucleic acids and drugs to ocular tissues including retina and cornea","volume":"16","author":"Johnson","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.visres.2009.08.028","article-title":"Cell penetrating peptide POD mediates delivery of recombinant proteins to retina, cornea and skin","volume":"50","author":"Johnson","year":"2010","journal-title":"Vis. Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1111\/j.1582-4934.2009.00786.x","article-title":"Cell-penetrating peptide TAT-mediated delivery of acidic FGF to retina and protection against ischemia-reperfusion injury in rats","volume":"14","author":"Wang","year":"2010","journal-title":"J. Cell Mol. Med."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Ozaki, T., Nakazawa, M., Yamashita, T., and Ishiguro, S. (2015). Delivery of Topically Applied Calpain Inhibitory Peptide to the Posterior Segment of the Rat Eye. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130986"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Ozaki, T., Ishiguro, S., Hirano, S., Baba, A., Yamashita, T., Tomita, H., and Nakazawa, M. (2013). Inhibitory peptide of mitochondrial mu-calpain protects against photoreceptor degeneration in rhodopsin transgenic S334ter and P23H rats. PLoS ONE, 8.","DOI":"10.1371\/annotation\/7a8aaf1d-e968-4b39-abb0-867d6078b2af"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1016\/j.bbadis.2012.07.018","article-title":"Intravitreal injection or topical eye-drop application of a mu-calpain C2L domain peptide protects against photoreceptor cell death in Royal College of Surgeons\u2019 rats, a model of retinitis pigmentosa","volume":"1822","author":"Ozaki","year":"2012","journal-title":"Biochim. Biophys. Acta"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/7\/1071\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:08:22Z","timestamp":1760123302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/7\/1071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,1]]},"references-count":161,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["cells12071071"],"URL":"https:\/\/doi.org\/10.3390\/cells12071071","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,1]]}}}