REVIEW ––––––––––––––––––––––––––––––––––––––––– Nanotechnology in ophthalmology Marco A. Zarbin,* MD, PhD; Carlo Montemagno, { PhD; James F. Leary, { PhD; Robert Ritch, § MD ABSTRACT N RE ´ SUME ´ Nanotechnology involves the creation and use of materials and devices at the size scale of intracellular structures and molecules, and involves systems and constructs in the order of ,100 nm. The aim of nanomedicine is the comprehensive monitoring, control, construction, repair, defence, and improvement of human biological systems at the molecular level, using engineered nanodevices and nanostructures that operate massively in parallel at the single-cell level, ultimately to achieve medical benefit. In this review we consider general principles of nanotechnology as applied to nanomedicine (e.g., biomimicry and pseudointelligence). Some applications of nanotechnology to ophthalmology are described (including treatment of oxidative stress; measurement of intraocular pressure; theragnostics; use of nanoparticles to treat choroidal new vessels, prevent scarring after glaucoma surgery, and treat retinal degenerative disease with gene therapy; prosthetics; and regenerative nanomedicine). Nanotechnology will revolutionize our approach to current therapeutic challenges (e.g., drug delivery, postoperative scarring) and will enable us to address currently unsolvable problems (e.g., sight-restoring therapy for patients with retinal degenerative disease). Obstacles to the incorporation of nanotechnology remain, such as safe manufacturing techniques and unintended biological consequences of nanomaterial use. These obstacles are not insurmountable, and revolutionary treatments for ophthalmic diseases are expected to result from this burgeoning field. La nanotechnologie implique la cre ´ation et l’utilisation de mate ´riaux et d’appareils a ` l’e ´chelle des structures et des mole ´cules intracellulaires et comporte des syste `mes et des concepts de l’ordre de ,100 nm. La nanome ´decine a globalement pour but le monitorage, le contro ˆ le, la construction, la re ´paration, la de ´fense et l’ame ´lioration des syste `mes biologiques humains au niveau mole ´culaire et l’utilisation de nanoappareils et de nanostructures, conc ¸us pour fonction- ner massivement en paralle `le au niveau d’une seule cellule et finalement donner de bons re ´sultats me ´dicaux. Cet article traite des principes ge ´ne ´raux de l’application de la nanotechnologie a ` la nanome ´decine (e.g., biomime ´tique et pseudoin- telligence). Certaines applications de la nanotechnologie a ` l’ophtalmologie y sont de ´crites (notamment le traitement du stress oxydatif, la mesure de la pression intraoculaire, le the ´ragnostic, l’utilisation de nanoparticules pour traiter les nouveaux vaisseaux choroı ¨diens, la pre ´vention de la cicatrisation apre `s la chirurgie du glaucome et le traitement de la maladie de ´ge ´ne ´rative de la re ´tine par the ´rapie ge ´ne ´tique, la prothe ´tique et la nanome ´decine re ´ge ´ne ´ratrice). La nano- technologie va re ´volutionner notre fac ¸on d’aborder les de ´fis the ´rapeutiques courants (e.g., l’administration des me ´dica- ments, la cicatrisation postope ´ratoire) et nous permettra d’aborder des proble `mes actuellement insolubles (e.g., la restauration de la vue des patients atteints d’une maladie de ´ge ´ne ´rative de la re ´tine). Les obstacles a ` l’inte ´gration de la nanotechnologie demeurent, telles la se ´curite ´ des techniques de fabrication et les conse ´quences biologiques non voulues de l’utilisation de nanomate ´riaux. Ces obstacles ne sont cependant pas insurmontables et on pre ´voit que de ce domaine en pleine expansion e ´maneront des traitements re ´volutionnaires pour les maladies oculaires. W e have recently reviewed the topic, nanomedicine in ophthalmology. 1 In this article, we recapitulate some aspects of that review and provide additional exam- ples of applications of nanotechnology (and related disci- plines) to ophthalmology. NANOTECHNOLOGY Nanotechnology involves the creation and use of mate- rials and devices at the size scale of intracellular structures and molecules, and involves systems and constructs in the order of ,100 nm. (For comparison, a typical man is 1.6 m [1.6 billion nm] tall; an erythrocyte is 7 mm [7 6 10 3 nm] wide; a strand of DNA is 2 nm wide.) Nanomachines are highly efficient. 2 When organized in massively parallel structures, for example, nanomotors are capable of generating large forces (e.g., muscles that move massive animals such as whales) and large electrical currents (such as those generated by the Hunter’s organ of electric eels). These same structures can also direct delicate processes (e.g., ion transport, chromosomal migration during mitosis). In addition to being highly efficient, nanomachines typi- cally have long operational half-lives and are mass pro- duced easily. One example of a biological nanomachine is From *the Institute of Ophthalmology and Visual Science, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, N.J.; { the College of Engineering, University of Cincinnati, OH; { Purdue University, West Lafayette, Ind.; and § the New York Eye & Ear Infirmary, and the New York Medical College, Valhalla, N.Y. Presented in part at the Next Generation Eye Surgery, Device and Drug Delivery Symposium in Toronto, Ont., October, 17, 2009 Originally received Aug. 10, 2010 Accepted Aug. 13, 2010 Published online Sep. 22, 2010 Correspondence to Marco A. Zarbin, MD, Institute of Ophthalmology and Visual Science, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Room 6155, Doctors Office Center, 90 Bergen St., Newark, NJ 07103; zarbin@umdnj.edu This article has been peer-reviewed. Cet article a e ´te ´e ´value ´ par les pairs. Can J Ophthalmol 2010;45:457–76 doi:10.3129/i10-090 CAN J OPHTHALMOL—VOL. 45, NO. 5, 2010 457