Atomic force microscopy in the study of retinal structure

Gamidov A.A.; Baryshev K.V.; Perevozchikov K.A.; Surnina Z.V.

doi:https://doi.org/10.17116/oftalma2020136042251

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Abstract:

The review addresses the current state of atomic force microscopy (AFM) usage in ophthalmology. Briefly presented here are the history of the development of AFM, principles and modes of operation, its advantages, disadvantages, as well as a comparison with other types of microscopy. The review describes the capabilities of AFM in visualization of various structures of the eye. A significant part of the review is devoted to the study of the retina, which arouses great interest among researchers. In particular, the possibilities of AFM for visualization at the submicron level of various structures in the retina, such as the internal limiting membrane, membrane cells, Müller cells, retinal pigment epithelium in their normal state and in the presence of a pathology (age-related macular degeneration, diabetes mellitus) were reviewed. In addition, several study papers were analyzed, providing a base for the judgement of the mechanical properties of said structures. An AFM study of the visual pigment rhodopsin helped identify its dimeric structure. The stability of the rhodopsin molecule was proved to be determined by the degree of strength of its individual segments connected to each other. The AFM method is a highly accurate method that helps solve many fundamental and practical problems, particularly in ophthalmology.

Keywords:

atomic force microscopy

ophthalmology

eye

retina

Authors:

Gamidov A.A.

Krasnov Research Institute of Eye Diseases

ORCID: 0000-0002-9192-449X

Baryshev K.V.

Research Institute of Eye Diseases

Perevozchikov K.A.

Research Institute of Eye Diseases

Surnina Z.V.

Krasnov Research Institute of Eye Diseases

ORCID: 0000-0001-5692-1800

Received:

15.05.2020

Accepted:

25.05.2020

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References:

Binnig G, Rohrer H, Gerber C, Weibel E. Surface studies by scanning tunneling microscopy. Physical Review Letters. 1982;49(1):57-61. https://doi.org/10.1103/PhysRevLett.49.57
Gerber C, Binnig G, Fuchs H, Marti O, Rohrer H. Scanning tunneling microscope combined with a scanning electron microscope. Review of Scientific Instruments. 1986;57(2):221-224. https://doi.org/10.1063/1.1138973
Binnig G, Quate CF, Gerber C. Atomic force microscope. Physical Review Letters. 1986;56:930-933. https://doi.org/10.1103/PhysRevLett.56.930
Ziebarth NM, Rico F, Moy VT. Structural and Mechanical Mechanisms of Ocular Tissues Probed by AFM. In: Bushan B, ed. Scanning Probe Microscopy in Nanoscience and Nanotechnology. Berlin Heidelberg: Springer; 2010. https://doi.org/10.1007/978-3-642-03535-7_11
Baum OI, Omelchenko AI, Kasyanenko EM, Skidanov RV, Kazanskij NL, Sobol EN, Bolshunov AV, Siplivyj VI, Osipyan GA, Gamidov AA, Avetisov SE. New biophotonics methods for improving efficiency and safety of laser modification of the fibrous tunic of the eye. Vestnik oftal’mologii. 2018;134(5): 4-14. https://doi.org/10.17116/oftalma20181340514
Meller D, Peters K, Meller K. Human cornea and sclera studied by atomic force microscopy. Cell and Tissue Research. 1997;288(1):111-118. https://doi.org/10.1007/s004410050798
Abrams GA, Schaus SS, Goodman SL, Nealey PF, Murphy CJ. Nanoscale topography of the corneal epithelial basement membrane and Descemet’s membrane of the human. Cornea. 2000;19(1):57-64. https://doi.org/10.1097/00003226-200001000-00012
Lombardo M, De Santo MP, Lombardo G, Barberi R, Serrao S. Atomic force microscopy analysis of normal and photoablated porcine corneas. Journal of Biomechanics. 2006;39(14):2719-2724. https://doi.org/10.1016/j.jbiomech.2005.08.013
Nogradi A, Hopp B, Revesz K, Szabo G, Bor Z, Kolozsvari L. Atomic force microscopic study of the human cornea following excimer laser keratectomy. Experimental Eye Research. 2000;70:363-368. https://doi.org/10.1006/exer.1999.0795
Avetisov SE, Bol’shunov AV, Khomchik OV, Fyodorov AA, Siplivyj VI, Baum OI, Omelchenko AI, Shcherbakov EM, Panchenko VJa, Sobol EN. Laser-induced increase of scleral hydropermiability in the treatment of resistant forms open-angle glaucoma. Nacional’nyj zhurnal Glaukoma. 2015;14(2):5-13. (In Russ.). Accessed June 18, 2020. https://www.glaucomajournal.ru/jour/article/view/57/58#
Zharov VV, Lyalin AN, Karban OV, Perevozchikov PA, Samartseva NN, Konygin GN, Leesment SI. Scanning probe microscopy in the study of tissue regeneration during scleroplastic operations in ophthalmology. Poverhnost’. Rentgenovskie, sinhrotronnye i nejtronnye issledovaniya. 2009;10:69-74 (In Russ.).
Fullwood NJ, Hammiche A, Pollock HM, Hourston DJ, Song M. Atomic force microscopy of the cornea and sclera. Experimental Eye Research. 1995; 14(7):529-535. https://doi.org/10.3109/02713689508998399
Hendrickson A. Organization of the adult primate fovea. In: Penfold P., Provis J., eds. Macular Degeneration. Berlin Heidelberg: Springer; 2005. https://doi.org/10.1007/3-540-26977-0_1
Augusteyn RC. Growth of the lens: in vitro observations. Clinical and Experimental Optometry. 2008;91(3):226-239. https://doi.org/10.1111/j.1444-0938.2008.00255.x
Antunes A, Gozzo FV, Borella MI, Nakamura M, Safatle AMV, Barros PSM, Toma HE. Atomic force imaging of ocular tissues: morphological study of healthy and cataract lenses. In: Mendez-Vilas A, Diaz J, eds. Modern Research and Educational Topics in Microscopy. Formatex; 2007; 29-36. Accessed June 18, 2020. https://www.researchgate.net/publication/228555473_Atomic_force_imaging_of_ocular_tissues_morphological_study_of_healthy_and_cataract_lenses
Antunes A, Gozzo FV, Nakamura M, Safatle AM, Morelh˜ao SL, Toma HE, Barros PS. Analysis of the healthy rabbit lens surface using MAC mode atomic force microscopy. Micron. 2007;38(3):286-290. https://doi.org/10.1016/j.micron.2006.04.006
Candiello JE, Feola AJ, Elyaderani A, Friberg TR, Lin H. Biomechanical Properties of the Bruch’s Membrane: An Atomic Force Microscopy Study. Investigative Ophthalmology and Visual Science. 2005;46(13):1210.
To M, Goz A, Camenzind L, To M, Goz A, Camenzind L, Oertle P, Candiello J, Sullivan M, Henrich PB, Loparic M, Safi F, Eller A, Halfter W. Diabetes-induced morphological, biomechanical, and compositional changes in ocular basement membranes. Experimental Eye Research. 2013;116:298-307. https://doi.org/10.1016/j.exer.2013.09.011
Franze K, Francke M, Guenter K, Christ A, Körber N, Reichenbach A, Guck J. Spatial mapping of the mechanical properties of the living retina using scanning force microscopy. Soft Matter. 2011;7:3147-3154. https://doi.org/10.1039/C0SM01017K
Last JA, Russell P, Nealey PF, Murphy CJ. The Applications of Atomic Force Microscopy to Vision Science. Investigative Ophthalmology and Visual Science. 2010;51(12):6083-6094. https://doi.org/10.1167/iovs.10-5470
Lombardo M, De Santo MP, Lombardo G, Barberi R, Serrao S. Analysis of intraocular lens surface properties with atomic force microscopy. Journal of Cataract and Refractive Surgery. 2006;32(8):1378-1384. https://doi.org/10.1016/j.jcrs.2006.02.068
Ohnishi Y, Yoshitomi T, Sakamoto T, Fujisawa K, Ishibashi T. Evaluation of cellular adhesions on silicone and poly(methyl methacrylate) intraocular lenses in monkey eyes; an electron microscopic study. Journal of Cataract and Refractive Surgery. 2001;27:20362-040. https://doi.org/10.1016/s0886-3350(01)00961-0
Gonzalez-Meijome JM, Lopez-Alemany A, Almeida JB, Parafita MA, Refojo MF. Microscopic observation of unworn siloxane-hydrogel soft contact lenses by atomic force microscopy. Journal of Biomedical Materials Research. Part B, Applied Biomaterials. 2005;76(2):412-418. https://doi.org/10.1002/jbm.b.30387
Chalupa E, Swarbrick HA, Holden BA, Sjöstrand J. Severe corneal infections associated with contact lens wear. Ophthalmology. 1987;94(1):17-22. https://doi.org/10.1010/S0161-6420(87)33513-4
Baguet J, Sommer F, Duc TM. Imaging surfaces of hydrophilic contact lenses with the atomic force microscope. Biomaterials. 1993;14(4):279-284. https://doi.org/10.1016/0142-9612(93)90118-l
Guryca V, Hobzová R, Prádný M, Sirc J, Michálek J. Surface morphology of contact lenses probed with microscopy techniques. Contact Lens and Anterior Eye. 2007;30(4):215-222. https://doi.org/10.1016/j.clae.2007.02.010
Liu B, Kilpatrick JI, Lukasz B, Jarvis SP, McDonnell F, Wallace DM, Clark AF, O’Brien CJ. Increased Substrate Stiffness Elicits a Myofibroblastic Phenotype in Human Lamina Cribrosa Cells. Investigative Ophthalmology and Visual Science. 2018;59(2):803-814. https://doi.org/10.1167/iovs.17-22400
Mallick SB, Ivanisevic A. Study of the morphological and adhesion properties of collagen fibers in the Bruch’s membrane. Journal of Physical Chemistry. B. 2005;109(41):19052-19055. https://doi.org/10.1021/jp053605w
Mallick SB, Bhagwandin S, Ivanisevic A. Characterization of collagen fibers in Bruch’s membrane using chemical force microscopy. Analytical and Bioanalytical Chemistry. 2006;386(3):652-657. https://doi.org/10.1007/s00216-006-0538-7
Sarna M, Olchawa M, Zadlo A, Wnuk D, Sarna T. The nanomechanical role of melanin granules in the retinal pigment epithelium. Nanomedicine: Nanotechnology, Biology and Medicine. 2017;3(3):801-807. https://doi.org/10.1016/j.nano.2016.11.020
Guo S, Hong L, Akhremitchev BB, Simon JD. Surface Elastic Properties of Human Retinal Pigment Epithelium Melanosomes. Photochemistry and Photobiology. 2008;84(3):671-678. https://doi.org/10.1111/j.1751-1097.2008.00331.x
Biasutto L, Chiechi A, Couch R, Liotta LA, Espina V. Retinal pigmentepithelium (RPE) exosomes contain signaling phosphoproteins affected by oxidativestress. Experimental Cell Research. 2013;319(13):2113-2123. https://doi.org/10.1016/j.yexcr.2013.05.005
Halfter W, Willem M, Mayer U. Basement membrane-dependent survival of retinal ganglion cells. Investigative Ophthalmology and Visual Science. 2005; 46(3):1000-1009. https://doi.org/10.1167/iovs.04-1185
Park S, Lee YJ. Nano-mechanical compliance of Müller cells investigated by atomic force microscopy. International Journal of Biological Sciences. 2013;9(7):702-706. https://doi.org/10.7150/ijbs.6473
MacDonald RB, Randlett O, Oswald J, Yoshimatsu T, Franze K, Harris WA. Müller glia provide essential tensile strength to the developing retina. Journal of Cell Biology. 2015;210(7):1075-1083. https://doi.org/10.1083/jcb.201503115
Yang X, Scott HA, Monickaraj F, Xu J, Ardekani S, Nitta CF, Cabrera A, McGuire PG, Mohideen U, Das A, Ghosh K. Basement membrane stiffening promotes retinal endothelial activation associated with diabetes. FASEB Journal. 2016;30(2):601-611. https://doi.org/10.1096/fj.15-277962
Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A, Palczewski K. Atomic-force microscopy: rhodopsin dimers in native disc membranes. Nature. 2003;421(6919):127-128. https://doi.org/10.1038/421127a
Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A. Palczewski K. The G protein-coupled receptor rhodopsin in the native membrane. FEBS Letters. 2004;564(3):281-288. https://doi.org/10.1016/S0014-5793(04)00194-2
Fotiadis D, Jastrzebska B, Philippsen A, Müller DJ, Palczewski K, Engel A. Structure of the rhodopsin dimer: a working model for G-protein-coupled receptors. Current Opinion in Structural Biology. 2006;16(2):252-259. https://doi.org/10.1016/j.sbi.2006.03.013
Sergeev SA. Organotipicheskaya kul’tura setchatki glaza kak model’ dlya ocenki effektivnosti transplantacii kletok: dis. ... kand. boil nauk. M. 2011. (In Russ). https://www.bio.msu.ru/res/Dissertation/393/DOC_FILENAME/sergeev.pdf
Alhasawi AA. Microstructural Imaging of the Eye and Mechanical Mapping of Retinal Tissue using Atomic Force Microscopy (AFM). Master’s Thesis, Memorial University of Newfoundland, 2016. Accessed June 18, 2020. https://research.library.mun.ca/id/eprint/12124