American Journal of Ophthalmology
Volume 150, Issue 2 , Pages 144-162.e2 , August 2010

Nanomedicine in Ophthalmology: The New Frontier

  • Marco A. Zarbin

      Affiliations

    • Institute of Ophthalmology and Visual Science, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey
    • Corresponding Author InformationInquiries to Marco A. Zarbin, 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
  • ,
  • Carlo Montemagno

      Affiliations

    • College of Engineering, University of Cincinnati, Cincinnati, Ohio
  • ,
  • James F. Leary

      Affiliations

    • Purdue University, West Lafayette, Indiana
  • ,
  • Robert Ritch

      Affiliations

    • New York Eye & Ear Infirmary, New York, New York

,Accepted 10 March 2010.

References 

  1. Haglund EM, Seale-Goldsmith M-M, Leary JF. Design of multifunctional nanomedical systems. Ann Biomed Eng. 2009;37:2048–2063
  2. Seale M-M, Leary JF. Nanobiosystems. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009;1:553–567
  3. Prow T, Grebe R, Merges C, et al. Nanoparticle tethered antioxidant response element as a biosensor for oxygen induced toxicity in retinal endothelial cells. Mol Vis. 2006;12:616–625
  4. Prow T, Smith JN, Grebe R, et al. Construction, gene delivery, and expression of DNA tethered nanoparticles. Mol Vis. 2006;12:606–615
  5. Feynman R. There's plenty of room at the bottom. Eng Sci. 1960;23:22–36
  6. Ball P. High-density memory: a switch in time. Nature. 2007;445:362–363
  7. Freitas RA. What is nanomedicine?. Nanomedicine. 2005;1:2–9
  8. Morrow KJ, Bawa R, Wei C. Recent advances in basic and clinical nanomedicine. Med Clin North Am. 2007;91:805–843
  9. Prow T, Salazar JH, Rose WA, et al. Nanomedicine-nanoparticles, molecular biosensors and targeted gene/drug delivery for combined single-cell diagnostics and therapeutics. Proc SPIE. 2004;5318:1–11
  10. Prow T, Rose WA, Wang NA, Reece LM, Lvov Y, Leary JF. Biosensor-controlled gene therapy/drug delivery with nanoparticles for nanomedicine. Proc SPIE. 2005;5692:199–208
  11. Seale M, Haglund E, Cooper CL, Reece LM, Leary JF. Design of programmable mulitlayered nanoparticles with in situ manufacture of therapeutic genes for nanomedicine. Proc SPIE. 2007;6430:643003-1-7
  12. Banghart M, Borges K, Isacoff E, Trauner D, Kramer RH. Light-activated ion channels for remote control of neuronal firing. Nat Neurosci. 2004;7:1381–1386
  13. Volgraf M, Gorostiza P, Numano R, Kramer RH, Isacoff EY, Trauner D. Allosteric control of an ionotropic glutamate receptor with an optical switch. Nat Chem Biol. 2006;2:47–52
  14. Szobota S, Gorostiza P, Del Bene F, et al. Remote control of neuronal activity with a light-gated glutamate receptor. Neuron. 2007;54:535–545
  15. Barnes CP, Sell SA, Boland ED, Simpson DG, Bowlin GL. Nanofiber technology: designing the next generation of tissue engineering scaffolds. Adv Drug Deliv Rev. 2007;59:1413–1433
  16. Causa F, Netti PA, Ambrosio L. A multi-functional scaffold for tissue regeneration: The need to engineer a tissue analogue. Biomaterials. 2007;28:5093–5099
  17. Goldberg M, Langer R, Jia X. Nanostructured materials for applications in drug delivery and tissue engineering. J Biomater Sci Polym Ed. 2007;18:241–268
  18. Quondamatteo F. Assembly, stability and integrity of basement membranes in vivo. Histochem J. 2002;34:369–381
  19. Weigel T, Schinkel G, Lendlein A. Design and preparation of polymeric scaffolds for tissue engineering. Expert Rev Med Devices. 2006;3:835–851
  20. Sretavan DW, Chang W, Hawkes E, Keller C, Kliot M. Microscale surgery on single axons. Neurosurgery. 2005;57:635–646
  21. Tao S, Young C, Redenti S, et al. Survival, migration and differentiation of retinal progenitor cells transplanted on micro-machined poly(methyl methacrylate) scaffolds to the subretinal space. Lab Chip. 2007;7:695–701
  22. Ferreira L, Karp JM, Nobre L, Langer R. New opportunities: the use of nanotechnologies to manipulate and track stem cells. Cell Stem Cell. 2008;3:136–146
  23. Lin YM, Avouris P. Strong suppression of electrical noise in bilayer graphene nanodevices. Nano Lett. 2008;8(8):2119–2125
  24. Deshpande S, Patil S, Kuchibhatla SV, Seal S. Size dependency variation in lattice parameter and valency states in nanocrystalline cerium oxide. Appl Phys Lett. 2005;87:133113
  25. Tsunekawa S, Sahara R, Kawazoe Y, Ishikawa K. Lattice relaxation of monosize CeO2-x nanocrystalline particles. Appl Surf Sci. 1999;152:53–56
  26. Chen J, Patil S, Seal S, McGinnis JF. Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides. Nat Nanotechnol. 2006;1:142–150
  27. Shen JK, Dong A, Hackett SF, Bell WR, Green WR, Campochiaro PA. Oxidative damage in age-related macular degeneration. Histol Histopathol. 2007;22:1301–1308
  28. Zarbin MA. Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol. 2004;122:598–614
  29. Brownlee M. A radical explanation for glucose-induced beta cell dysfunction. J Clin Invest. 2003;112:1788–1790
  30. Yorek MA. The role of oxidative stress in diabetic vascular and neural disease. Free Radic Res. 2003;37:471–480
  31. Komeima K, Rogers BS, Campochiaro PA. Antioxidants slow photoreceptor cell death in mouse models of retinitis pigmentosa. J Cell Physiol. 2007;213:809–815
  32. Kothari ML, Mehta LA. Non-identicality of monozygous twins. J Postgrad Med. 1985;31:1–4
  33. Gringras P, Chen W. Mechanisms for differences in monozygous twins. Early Hum Dev. 2001;64:105–117
  34. Yanik MF, Cinar H, Cinar HN, Chisholm AD, Jin Y, Ben-Yakar A. Neurosurgery: functional regeneration after laser axotomy. Nature. 2004;432:822
  35. Wei C, Wei W, Morris M, Kondo E, Gorbounov M, Tomalia DA. Nanomedicine and drug delivery. Med Clin North Am. 2007;91:863–870
  36. Dresher RP, Irazoqui PP. A compact nanopower low output impedance CMOS operational amplifier for wireless intraocular pressure recordings. Conf Proc IEEE Eng Med Biol Soc. 2007;2007:6056–6059
  37. Pan T, Brown JD, Ziaie B. An artificial nano-drainage implant (ANDI) for glaucoma treatment. Conf Proc IEEE Eng Med Biol Soc. 2006;1:3174–3177
  38. Chu TC, He Q, Potter DE. Biodegradable calcium phosphate nanoparticles as a new vehicle for delivery of a potential ocular hypotensive agent. J Ocul Pharmacol Ther. 2002;18:507–514
  39. Kassem MA, Abdel Rahman AA, Ghorab MM, Ahmed MB, Khalil RM. Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs. Int J Pharm. 2007;340:126–133
  40. Dugan LL, Turetsky DM, Du C, et al. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci U S A. 1997;94:9434–9439
  41. Dugan LL, Lovett EG, Quick KL, Lotharius J, Lin TT, O'Malley KL. Fullerene-based antioxidants and neurodegenerative disorders. Parkinsonism Relat Disord. 2001;7:243–246
  42. Papp A, Nemeth I, Karg E, Papp E. Glutathione status in retinopathy of prematurity. Free Radic Biol Med. 1999;27:738–743
  43. Kroto HW, Heath JR, O'Brien SC, Curl RF, Smalley RE. C60: Buckminsterfullerene. Nature. 1985;318:162–163
  44. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965;13:238–252
  45. Hallberg D, Schuberth O, Wretlind A. Experimental and clinical studies with fat emulsion for intravenous nutrition. Nutr Dieta Eur Rev Nutr Diet. 1966;8:245–281
  46. Bondi ML, Craparo EF, Giammona G, et al. Nanostructured lipid carriers-containing anticancer compounds: preparation, characterization, and cytotoxicity studies. Drug Deliv. 2007;14:61–67
  47. Yuan XB, Yuan YB, Jiang W, et al. Preparation of rapamycin-loaded chitosan/PLA nanoparticles for immunosuppression in corneal transplantation. Int J Pharm. 2008;349:241–248
  48. Prow TW, Bhutto I, Kim SY, et al. Ocular nanoparticle toxicity and transfection of the retina and retinal pigment epithelium. Nanomedicine. 2008;4:340–349
  49. Zhang R, He R, Qian J, Guo J, Xue K, Yuan Y-F. Treatment of experimental autoimmune uveoretinitis with intravitreal injection of tacrolimus (FK506) encapsulated in liposomes. Invest Ophthalmol Vis Sci. 2010;Forthcoming
  50. Ferreira L, Park H, Choe H, Kohane D, Langer R. Human embryoid bodies containing nano- and micro-particulate delivery vehicles. Adv Mater. 2008;20:2285–2291
  51. Sakai T, Kuno N, Takamatsu F, et al. Prolonged protective effect of basic fibroblast growth factor-impregnated nanoparticles in Royal College of Surgeons rats. Invest Ophthalmol Vis Sci. 2007;48:3381–3387
  52. Jiang C, Moore MJ, Zhang X, Klassen H, Langer R, Young M. Intravitreal injections of GDNF-loaded biodegradable microspheres are neuroprotective in a rat model of glaucoma. Mol Vis. 2007;13:1783–1792
  53. Tomalia DA, Reyna LA, Svenson S. Dendrimers as multi-purpose nanodevices for oncology drug delivery and diagnostic imaging. Biochem Soc Trans. 2007;35:61–67
  54. Hahn U, Gorka M, Vogtle F, et al. Light-harvesting dendrimers: efficient intra- and intermolecular energy-transfer processes in a species containing 65 chromophoric groups of four different types. Angew Chem Int Ed Engl. 2002;41:3595–35983514
  55. Marano RJ, Toth I, Wimmer N, Brankov M, Rakoczy PE. Dendrimer delivery of an anti-VEGF oligonucleotide into the eye: a long-term study into inhibition of laser-induced CNV, distribution, uptake and toxicity. Gene Ther. 2005;12:1544–1550
  56. Vandamme TF, Brobeck L. Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide. J Control Release. 2005;102:23–38
  57. Ideta R, Tasaka F, Jang WD, et al. Nanotechnology-based photodynamic therapy for neovascular disease using a supramolecular nanocarrier loaded with a dendritic photosensitizer. Nano Lett. 2005;5:2426–2431
  58. Glover DJ, Lipps HJ, Jans DA. Towards safe, non-viral therapeutic gene expression in humans. Nat Rev Genet. 2005;6:299–310
  59. Kutsuzawa K, Chowdhury EH, Nagaoka M, Maruyama K, Akiyama Y, Akaike T. Surface functionalization of inorganic nano-crystals with fibronectin and E-cadherin chimera synergistically accelerates trans-gene delivery into embryonic stem cells. Biochem Biophys Res Commun. 2006;350:514–520
  60. Pack DW, Hoffman AS, Pun S, Stayton PS. Design and development of polymers for gene delivery. Nat Rev Drug Discov. 2005;4:581–593
  61. Incani V, Tunis E, Clements BA, et al. Palmitic acid substitution on cationic polymers for effective delivery of plasmid DNA to bone marrow stromal cells. J Biomed Mater Res A. 2007;81:493–504
  62. Farjo R, Skaggs J, Quiambao AB, Cooper MJ, Naash MI. Efficient non-viral ocular gene transfer with compacted DNA nanoparticles. PLoS ONE. 2006;1:e38
  63. Konstan MW, Davis PB, Wagener JS, et al. Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete cystic fibrosis transmembrane regulator reconstitution. Hum Gene Ther. 2004;15:1255–1269
  64. Mo Y, Barnett ME, Takemoto D, Davidson H, Kompella UB. Human serum albumin nanoparticles for efficient delivery of Cu, Zn superoxide dismutase gene. Mol Vis. 2007;13:746–757
  65. Cai X, Conley S, Naash M. Nanoparticle applications in ocular gene therapy. Vision Res. 2008;48:319–324
  66. Cai X, Nash Z, Conley SM, Fliesler SJ, Cooper MJ, Naash MI. A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles. PLoS ONE. 2009;4:e5290
  67. Jani PD, Singh N, Jenkins C, et al. Nanoparticles sustain expression of Flt intraceptors in the cornea and inhibit injury-induced corneal angiogenesis. Invest Ophthalmol Vis Sci. 2007;48:2030–2036
  68. Bejjani RA, BenEzra D, Cohen H, et al. Nanoparticles for gene delivery to retinal pigment epithelial cells. Mol Vis. 2005;11:124–132
  69. Kim W, Ng JK, Kunitake ME, Conklin BR, Yang P. Interfacing silicon nanowires with mammalian cells. J Am Chem Soc. 2007;129:7228–7229
  70. Kostarelos K, Lacerda L, Pastorin G, et al. Cellular uptake of functionalized carbon nanotubes is independent of functional group and cell type. Nat Nanotechnol. 2007;2:108–113
  71. Bianco A, Kostarelos K, Prato M. Applications of carbon nanotubes in drug delivery. Curr Opin Chem Biol. 2005;9:674–679
  72. Nune SK, Gunda P, Thallapally PK, Lin Y-Y, Laird Forrest M, Berkland CJ. Nanoparticles for biomedical imaging. Expert Opin Drug Deliv. 2009;6:1175–1194
  73. Boisselier E, Astruc D. Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev. 2009;38:1759–1782
  74. Elghanian R, Storhoff JJ, Mucic RC, Letsinger RL, Mirkin CA. Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. Science. 1997;277:1078–1081
  75. Reimer P, Balzer T. Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications. Eur Radiol. 2003;13:1266–1276
  76. Wang YX, Hussain SM, Krestin GP. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol. 2001;11:2319–2331
  77. Hsiao JK, Tai MF, Chu HH, et al. Magnetic nanoparticle labeling of mesenchymal stem cells without transfection agent: cellular behavior and capability of detection with clinical 1.5 T magnetic resonance at the single cell level. Magn Reson Med. 2007;58:717–724
  78. Zhu J, Zhou L, XingWu F. Tracking neural stem cells in patients with brain trauma. N Engl J Med. 2006;355:2376–2378
  79. Guzman R, Uchida N, Bliss TM, et al. Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI. Proc Natl Acad Sci U S A. 2007;104:10211–10216
  80. Michalet X, Pinaud FF, Bentolila LA, et al. Quantum dots for live cells, in vivo imaging, and diagnostics. Science. 2005;307:538–544
  81. Lei Y, Tang H, Yao L, Yu R, Feng M, Zou B. Applications of mesenchymal stem cells labeled with Tat peptide conjugated quantum dots to cell tracking in mouse body. Bioconjug Chem. 2008;19:421–427
  82. Slotkin JR, Chakrabarti L, Dai HN, et al. In vivo quantum dot labeling of mammalian stem and progenitor cells. Dev Dyn. 2007;236:3393–3401
  83. Derfus AM, Chan WCW, Bhatia SN. Probing the cytotoxicity of semiconductor quantum dots. Adv Mater. 2004;4:11–18
  84. Lovric J, Cho SJ, Winnik FM, Maysinger D. Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. Chem Biol. 2005;12:1227–1234
  85. Takeda A, Baffi JZ, Kleinman ME, et al. CCR3 is a target for age-related macular degeneration diagnosis and therapy. Nature. 2009;460:225–230
  86. Cohen-Karni T, Timko BP, Weiss LE, Lieber CM. Flexible electrical recording from cells using nanowire transistor arrays. Proc Natl Acad Sci U S A. 2009;106:7309–7313
  87. Chen P-J, Rodger DC, Saati S, Humayun MS, Tai Y-C. Microfabricated implantable parylene-based wireless passive intraocular pressure sensors. J Microelectromech Syst. 2008;17:1342–1351
  88. Mohammed JS, DeCoster MA, McShane MJ. Micropatterning of nanoengineered surfaces to study neuronal cell attachment in vitro. Biomacromolecules. 2004;5:1745–1755
  89. Mossman K, Groves J. Micropatterned supported membranes as tools for quantitative studies of the immunological synapse. Chem Soc Rev. 2007;36:46–54
  90. Ainslie KM, Tao SL, Popat KC, Desai TA. In vitro immunogenicity of silicon-based micro- and nanostructured surfaces. ACS Nano. 2008;2:1076–1084
  91. Curtis AS, Gadegaard N, Dalby MJ, Riehle MO, Wilkinson CD, Aitchison G. Cells react to nanoscale order and symmetry in their surroundings. IEEE Trans Nanobioscience. 2004;3:61–65
  92. Dalby MJ, Riehle MO, Sutherland DS, Agheli H, Curtis AS. Changes in fibroblast morphology in response to nano-columns produced by colloidal lithography. Biomaterials. 2004;25:5415–5422
  93. Gallagher JO, McGhee KF, Wilkinson CD, Riehle MO. Interaction of animal cells with ordered nanotopography. IEEE Trans Nanobioscience. 2002;1:24–28
  94. Huang NF, Patel S, Thakar RG, et al. Myotube assembly on nanofibrous and micropatterned polymers. Nano Lett. 2006;6:537–542
  95. Kim DH, Kim P, Suh KY, Choi SK, Lee SH, Kim B. Modulation of adhesion and growth of cardiac myocytes by surface nanotopography (27th Annual International Conference of the IEEE Engineering in Medicine and Biology Society). Conf Proc IEEE Eng Med Biol Soc. 2005;4091–4094
  96. Popat KC, Leoni L, Grimes CA, Desai TA. Influence of engineered titania nanotubular surfaces on bone cells. Biomaterials. 2007;28:3188–3197
  97. Yim EK, Reano RM, Pang SW, Yee AF, Chen CS, Leong KW. Nanopattern-induced changes in morphology and motility of smooth muscle cells. Biomaterials. 2005;26:5405–5413
  98. Scadden DT. The stem-cell niche as an entity of action. Nature. 2006;441:1075–1079
  99. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002;110
  100. Park J, Bauer S, von der Mark K, Schmuki P. Nanosize and vitality: TiO2 nanotube diameter directs cell fate. Nano Lett. 2007;7:1686–1691
  101. Chua KN, Chai C, Lee PC, et al. Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells. Biomaterials. 2006;27:6043–6051
  102. Dalby MJ, McCloy D, Robertson M, Wilkinson CD, Oreffo RO. Osteoprogenitor response to defined topographies with nanoscale depths. Biomaterials. 2006;27:1306–1315
  103. Park J, Bauer S, Schlegel KA, Neukam FW, von der Mark K, Schmuki P. TiO2 nanotube surfaces: 15 nm—an optimal length scale of surface topography for cell adhesion and differentiation. Small. 2009;5:666–671
  104. Jan E, Kotov NA. Successful differentiation of mouse neural stem cells on layer-by-layer assembled single-walled carbon nanotube composite. Nano Lett. 2007;7:1123–1128
  105. Pot SA, Liliensiek SJ, Myrna KE, et al. Nanoscale topography-induced modulation of fundamental cell behaviors of rabbit corneal keratocytes, fibroblasts, and myofibroblasts. Invest Ophthalmol Vis Sci. 2010;51:1373–1381
  106. Gullapalli VK, Sugino IK, Van Patten Y, Shah S, Zarbin MA. Impaired RPE survival on aged submacular human Bruch's membrane. Exp Eye Res. 2005;80:235–248
  107. Tezel TH, Del Priore LV. Repopulation of different layers of host human Bruch's membrane by retinal pigment epithelial cell grafts. Invest Ophthalmol Vis Sci. 1999;40:767–774
  108. Tezel TH, Del Priore LV, Berger AS, Kaplan HJ. Adult retinal pigment epithelial transplantation in exudative age-related macular degeneration. Am J Ophthalmol. 2007;143:584–595
  109. Del Priore LV, Kaplan HJ, Tezel TH, Hayashi N, Berger AS, Green WR. Retinal pigment epithelial cell transplantation after subfoveal membranectomy in age-related macular degeneration: clinicopathologic correlation. Am J Ophthalmol. 2001;131:472–480
  110. Mooney DJ, Vandenburgh H. Cell delivery mechanisms for tissue repair. Cell Stem Cell. 2008;2:205–213
  111. Silva GA, Czeisler C, Niece KL, et al. Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science. 2004;303:1352–1355
  112. Ellis-Behnke RG, Liang YX, You SW, et al. Nano neuro knitting: peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. Proc Natl Acad Sci U S A. 2006;103:5054–5059
  113. Neely WL, Redenti S, Klassen H, et al. A microfabricated scaffold for retinal progenitor cell grafting. Biomaterials. 2008;29:418–426
  114. Redenti S, Tao S, Yang J, et al. Retinal tissue engineering using mouse retinal progenitor cells and a novel biodegradable, thin-film poly(e-caprolactone) nanowire scaffolds. J Ocul Biol Dis Infor. 2008;1:19–29
  115. Tao SL, Desai TA. Aligned arrays of biodegradable poly(epsilon-caprolactone) nanowires and nanofibers by template synthesis. Nano Lett. 2007;7:1463–1468
  116. Neeley WL, Redenti S, Klassen H, et al. A microfabricated scaffold for retinal progenitor cell grafting. Biomaterials. 2008;29:418–426
  117. Sundback CA, Shyu JY, Wang Y, et al. Biocompatibility analysis of poly(glycerol sebacate) as a nerve guide material. Biomaterials. 2005;26:5454–5464
  118. Beeley NR, Rossi JV, Mello-Filho PA, et al. Fabrication, implantation, elution, and retrieval of a steroid-loaded polycaprolactone subretinal implant. J Biomed Mater Res A. 2005;73:437–444
  119. Jones BW, Watt CB, Frederick JM, et al. Retinal remodeling triggered by photoreceptor degenerations. J Comp Neurol. 2003;464:1–16
  120. Milam AH, Li ZY, Fariss RN. Histopathology of the human retina in retinitis pigmentosa. Prog Retin Eye Res. 1998;17:175–205
  121. Lakhanpal RR, Yanai D, Weiland JD, et al. Advances in the development of visual prostheses. Curr Opin Ophthalmol. 2003;14:122–127
  122. Chen SJ, Mahadevappa M, Roizenblatt R, Weiland J, Humayun M. Neural responses elicited by electrical stimulation of the retina. Trans Am Ophthalmol Soc. 2006;104:252–259
  123. Choi SY, Sheng Z, Kramer RH. Imaging light-modulated release of synaptic vesicles in the intact retina: retinal physiology at the dawn of the post-electrode era. Vision Res. 2005;45:3487–3495
  124. Pennisi CP, Jensen PE, Zachar V, Greenbaum E, Yoshida K. Incorporation of photosynthetic reaction centers in the membrane of human cells: Toward a new tool for optical control of cell activity. Cell Mol Bioeng. 2009;2:156–165
  125. Kuritz T, Lee I, Owens ET, Humayun M, Greenbaum E. Molecular photovoltaics and the photoactivation of mammalian cells. IEEE Trans Nanobioscience. 2005;4:196–200
  126. Pennisi CP, Greenbaum E, Yoshida K. Spatial distribution of the electric potential from photosystem I reaction centers in lipid vesicles. IEEE Trans Nanobioscience. 2008;7:164–171
  127. Nagel G, Szellas T, Huhn W, et al. Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A. 2003;100:13940–13945
  128. Bi A, Cui J, Ma YP, et al. Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron. 2006;50:23–33
  129. Greenberg KP, Pham A, Delwig A, Werblin FS. Genetically reconstructed center-surround opponency by targeting channelrhodopsin-2 and halorhodopsin to ganglion cell somata and dendrites. Invest Ophthalmol Vis Sci. 2009;50:ARVO E-Abstract-3896
  130. Wei C, Nagai T, Wei W, et al. New advances in nanomedicine: diagnosis and preventive medicine. Med Clin North Am. 2007;91:871–879
  131. Helmchen F, Denk W. Deep tissue two-photon microscopy. Nat Methods. 2005;2:932–940
  132. Prow TW, Bhutto I, Grebe R, et al. Nanoparticle-delivered biosensor for reactive oxygen species in diabetes. Vision Res. 2008;48:478–485
  133. Sacconi L, O'Connor RP, Jasaitis A, Masi A, Buffelli M, Pavone FS. In vivo multiphoton nanosurgery on cortical neurons. J Biomed Opt. 2007;12:050502
  134. Ellis-Behnke RG, Teather LA, Schneider GE, So KF. Using nanotechnology to design potential therapies for CNS regeneration. Curr Pharm Des. 2007;13:2519–2528
  135. Wang BG, Halbhuber KJ. Corneal multiphoton microscopy and intratissue optical nanosurgery by nanojoule femtosecond near-infrared pulsed lasers. Ann Anat. 2006;188:395–409
  136. Leary SP, Liu CY, Apuzzo ML. Toward the emergence of nanoneurosurgery: part III—nanomedicine: targeted nanotherapy, nanosurgery, and progress toward the realization of nanoneurosurgery. Neurosurgery. 2006;58:1009–1026
  137. Fankhauser F, Niederer PF, Kwasniewska S, van der Zypen E. Supernormal vision, high-resolution retinal imaging, multiphoton imaging and nanosurgery of the cornea—a review. Technol Health Care. 2004;12:443–453
  138. Konig K. Robert Feulgen Prize Lecture (Laser tweezers and multiphoton microscopes in life sciences). Histochem Cell Biol. 2000;114:79–92
  139. Kim P, Lieber CM. Nanotube nanotweezers. Science. 1999;286:2148–2150
  140. Bhisitkul RB, Keller CG. Development of microelectromechanical systems (MEMS) forceps for intraocular surgery. Br J Ophthalmol. 2005;89:1586–1588
  141. Zhang LW, Monteiro-Riviere NA. Mechanisms of quantum dot nanoparticle cellular uptake. Toxicol Sci. 2009;110:138–155
  142. Hoet P, Legiest B, Geys J, Nemery B. Do nanomedicines require novel safety assessments to ensure their safety for long-term human use?. Drug Saf. 2009;32:625–636
  143. Magrez A, Kasas S, Salicio V, et al. Cellular toxicity of carbon-based nanomaterials. Nano Lett. 2006;6:1121–1125
  144. Zhu L, Chang DW, Dai L, Hong Y. DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. Nano Lett. 2007;7:3592–3597
  145. Sahoo SK, Labhasetwar V. Nanotech approaches to drug delivery and imaging. Drug Discov Today. 2003;8:1112–1120
  146. Lam R, Chen M, Pierstorff E, Huang H, Osawa E, Ho D. Nanodiamond-embedded microfilm devices for localized chemotherapeutic elution. ACS Nano. 2008;2:2095–2102

PII: S0002-9394(10)00233-3

doi: 10.1016/j.ajo.2010.03.019

American Journal of Ophthalmology
Volume 150, Issue 2 , Pages 144-162.e2 , August 2010