Skip to main content

Methodologies for Microscopic Characterization of Ocular Toxicity

  • Protocol
  • First Online:
Ocular Pharmacology and Toxicology

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

The eye is unique in being composed of different types of structures with various functions. One needs to be aware of these unique aspects and changes due to spontaneous, iatrogenic, or environmental conditions in order to detect toxicologic ocular changes. Since most ocular structures can be examined clinically, with or without specialized instruments, it is important to obtain microscopic correlates for clinical findings. This requires special attention to the techniques involved in obtaining good histologic sections for evaluation. Findings in standard histologic sections may be further characterized by use of immunohistochemistry or electron microscopy and appropriate terminology is important when identifying findings. This chapter will review all of these aspects of the microscopic examination for ocular toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Alves A, Metz A, Render J (2012) Microscopic and ultrastructural pathology of medical devices. In: Boutrand JP (ed) Biocompatability and performance of medical devices. Woodhead Pub, Cambridge

    Google Scholar 

  2. Short BG (2008) Safety evaluation of ocular drug delivery formulations: techniques and practical considerations. Toxicol Pathol 36:49–62

    PubMed  CAS  Google Scholar 

  3. Weiner AL, Gilger BC (2010) Advancements in ocular drug delivery. Vet Ophthalmol 13:395–406

    PubMed  CAS  Google Scholar 

  4. Wilkie DA, Wyman M (1991) Comparative anatomy and physiology of the mammalian eye. In: Hobson DW (ed) Dermal and ocular toxicology: fundamentals and methods. CRC, Boca Raton, FL

    Google Scholar 

  5. FDA (1998) Guidance for Industry and for the US FDA Reviewers and Staff. Aqueous Shunts—501(k) Submissions, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiologic Health. November 16

    Google Scholar 

  6. ISO 9394 (1998) Ophthalmic optics—contact lenses and contact lens care products—determination of biocompatibility by ocular study with rabbit eyes

    Google Scholar 

  7. ISO-11979–5 (2006) E Ophthalmic implants—intraocular lenses—part 5: biocompatability, ISO, Geneva, Switzerland

    Google Scholar 

  8. ISO-15798 (2010) Ophthalmic implants—ophthalmic viscosurgical devices—biocompatability, ISO, Geneva, Switzerland

    Google Scholar 

  9. McDonald TO, Seabaugh V, Shadduck JA et al (1987) Eye irritation. In: Marzulli FN, Maibach HI (eds) Dermatology. Hemisphere, Cambridge

    Google Scholar 

  10. Somps CJ, Greene N, Render JA (2009) A current practice for predicting ocular toxicity of systemically delivered drugs. Cutaneous Ocular Toxicol 28:1–18

    CAS  Google Scholar 

  11. Ramos M, Reilly CM, Bolon B (2011) Toxicological pathology of the retina and optic nerve. In: Bolon B, Butt MT (eds) Fundamental neuropathology for pathologists and toxicologists: principles and techniques. Wiley, Hoboken, NJ

    Google Scholar 

  12. Render JA, Dubielzig RR, Dunn DG, Hardisty JF, Moore RR (2009) Ocular collection protocol of the laboratory rabbit, dog and monkey. Exp Toxicol Pathol 61:403–404

    Google Scholar 

  13. Schafer KA, Render JA (2013) Toxicologic pathology of the eye: Histologic preparation and alterations of the anterior segment. In: Weir AB, Collins M (eds) Assessing ocular toxicology in laboratory animals, molecular and integrative toxicology. Springer Science + Business Media, New York

    Google Scholar 

  14. Teixeira LBC, Dubielzig RR (2013) Eye. In: Haschek WM, Rousseaux CG, Wallig MA (eds) Haschek and Rousseaux’s handbook of toxicologic pathology, 3rd edn. Elsevier, Missouri

    Google Scholar 

  15. Millichamp NJ (1992) Toxicity in specific ocular tissues. In: Chiou GCY (ed) Ophthalmic toxicology. Raven, New York

    Google Scholar 

  16. Millichamp NJ (1992) Factors affecting the interpretation of species differences in toxic responses of ocular tissues. In: Chiou GCY (ed) Ophthalmic toxicology. Raven, New York

    Google Scholar 

  17. Riley MV, Green K (1992) Comparative physiology and biochemistry of the eye. In: Hockwin O, Green K, Rubin LF (eds) Manual of oculotoxicity testing of drugs. Gustav Fischer, Stuttgart

    Google Scholar 

  18. Rubin LF (1992) Comparative anatomy of the eye. In: Hockwin O, Green K, Rubin LF (eds) Manual of oculotoxicity testing of drugs. Gustav Fischer, Stuttgart

    Google Scholar 

  19. Rubin LF, Weisse I (1992) Species differences relevant for ocular toxicity studies. In: Hockwin O, Green K, Rubin LF (eds) Manual of oculotoxicity testing of drugs. Gustav Fischer, Stuttgart

    Google Scholar 

  20. Schiavo DM (1992) Special topics about the use of laboratory animals in toxicology—an ophthalmoscopic assessment. In: Hockwin O, Green K, Rubin LF (eds) Manual of oculotoxicity testing of drugs. Gustav Fischer, Stuttgart

    Google Scholar 

  21. Weisse I (1992) Microscopic examination of the eye. In: Hockwin O, Green K, Rubin LF (eds) Manual of oculotoxicity testing of drugs. Gustav Fischer, Stuttgart

    Google Scholar 

  22. Harroff HH (1991) Pathological process of the eye related to chemical exposure. In: Hobson DW (ed) Dermal and ocular toxicology. Fundamentals and methods. CRC, Boca Raton, FL

    Google Scholar 

  23. Kuiper B, Boeve MH, Jansen T et al (1997) Ophthalmologic examination in systemic toxicity studies: an overview. Lab Anim 31:177–183

    PubMed  CAS  Google Scholar 

  24. Rubin LF (1974) Atlas of veterinary ophthalmoscopy. Lea & Febiger, Philadelphia, PA

    Google Scholar 

  25. Saunders LZ, Rubin LF (1975) Ophthalmic pathology of animals. S. Karger, New York

    Google Scholar 

  26. Vézina M (2012) Comparative ocular anatomy in commonly used laboratory animals. In: Weir AB, Collins M (eds) Assessing ocular toxicology in laboratory animals, molecular and integrative toxicology. Springer Science + Business Media, New York

    Google Scholar 

  27. Eglitis I (1964) The Glands. In: Prince JH (ed) The rabbit in eye research. Charles C. Thomas Pub, Springfield

    Google Scholar 

  28. Bellhorn RW (1980) Lighting in the animal environment. Lab Anim Sci 30:440–450

    PubMed  CAS  Google Scholar 

  29. Dureau P, Jeanny JC, Clerc B et al (1996) Long term light-induced retinal degeneration in the miniature pig. Mol Vis 2:7

    PubMed  CAS  Google Scholar 

  30. Herck HV, Baumans V, van der Craats NR et al (1992) Historical changes in the orbital region of rats after orbital puncture. Lab Anim 26:53–58

    PubMed  Google Scholar 

  31. McGee MA, Maronpot RR (1979) Harderian gland dacryoadenitis in rats resulting from orbital bleeding. Lab Anim Sci 29:639–641

    PubMed  CAS  Google Scholar 

  32. Noell WK, Albrecht R (1971) Irreversible effects on visible light on the retina: role of vitamin A. Science 172:76–79

    PubMed  CAS  Google Scholar 

  33. Organisaciak DT, Winkler BS (1994) Retinal light damage: practical and theoretical considerations. In: Chader G, Osborne N (eds) Progress Retinal Res. Pergammon, New York

    Google Scholar 

  34. Peiffer RL, Porter DP (1991) Light-induced retinal degeneration, rat. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals: eye and ear. Springer, Berlin

    Google Scholar 

  35. Render J, Schafer K, Altschuler R (2013) Special senses. In: Sahota PS, Popp JA, Hardisty JF, Gopinath C (eds) Toxicologic pathology in nonclinical safety assessment. CRC, Boca Raton, FL

    Google Scholar 

  36. Tanito M, Li F, Elliott MH et al (2007) Protective effect of TEMPOL derivatives against light-induced retinal damage in rats. Invest Ophthalmol Vis Sci 48:1900–1905

    PubMed  Google Scholar 

  37. Weisse I, Stotzer H, Seitz R (1974) Age- and light-dependent changes in the rat eye. Virchows Arch A Pathol Anat Histol 362:145–156

    PubMed  CAS  Google Scholar 

  38. Greenman DL, Bryant P, Kodell RL et al (1982) Influence of cage shelf level on retinal atrophy in mice. Lab Anim Sci 32:353–356

    PubMed  CAS  Google Scholar 

  39. Geiss V, Yoshitomo K (1999) Eyes. In: Maronpot RR, Boorman GA, Gaul BW (eds) Pathology of the mouse. Cache River, St. Louis, MO

    Google Scholar 

  40. Greaves P (2000) Histopathology of preclinical toxicity studies: interpretation and relevance in drug safety evaluation. Elsevier Science B.V., New York

    Google Scholar 

  41. Hubert MF, Gillet JP, Durand-Cavagna G (1994) Spontaneous retinal changes in Sprague Dawley rats. Lab Anim Sci 44:561–567

    PubMed  CAS  Google Scholar 

  42. Katsuta O, Shinomiya K, Mochizuki T (2008) Pseudopterygium: Unique conjunctival stricture observed in Japanese White rabbit. J Toxicol Pathol 21:239–241

    Google Scholar 

  43. Kuno H, Usui T, Eydelloth RS et al (1991) Spontaneous ophthalmic lesions in young Sprague–Dawley rats. J Vet Med Sci 53:607–614

    PubMed  CAS  Google Scholar 

  44. Lai YL, Jacoby RO, Jonas AM (1978) Age-related and light-associated retinal changes in Fischer rats. Invest Ophthalmol Vis Sci 17:634–638

    PubMed  CAS  Google Scholar 

  45. Moore CP, Dubielzig R, Glaza SM (1987) Anterior corneal dystrophy of American Dutch Belted rabbits: biomicroscopic and histopathologic findings. Vet Pathol 24:28–33

    PubMed  CAS  Google Scholar 

  46. O’Steen WK, Anderson KV, Shear CR (1974) Photoreceptor degeneration in albino rats: dependency on age. Invest Ophthalmol 13:334–339

    PubMed  Google Scholar 

  47. Schafer KA, Render JA (2013) Toxicologic pathology of the eye: alterations of the lens and posterior segment. In: Weir AB, Collins M (eds) Assessing ocular toxicology in laboratory animals, molecular and integrative toxicology. Springer Science + Business Media, New York

    Google Scholar 

  48. Shibuya K, Satou K, Sugimoto K et al (1999) Background data on spontaneous ophthalmic lesions in Crj:CD(SD)IGS rats. In: Matsuzawa T, Inoue H (eds) Biological reference data on CD(SD) IGS rats. Best Printing Co. Ltd., Yokohama

    Google Scholar 

  49. Sinha DP, Cartwright ME, Johnson RC (2006) Incidental mononuclear cell infiltrate in the uvea of cynomolgus monkeys. Toxicol Pathol 34:148–151

    PubMed  Google Scholar 

  50. Taradach C, Greaves P (1984) Spontaneous eye lesions in laboratory animals: incidence in relation to age. Crit Rev Toxicol 12:121–147

    PubMed  CAS  Google Scholar 

  51. Taradach C, Regnier B, Perraud J (1981) Eye lesions in Sprague–Dawley rats: type and incidence in relation to age. Lab Anim 15:285–287

    PubMed  CAS  Google Scholar 

  52. Tucker MJ (1997) Special sense organs and associated tissues. In: Tucker MJ (ed) Diseases of the Wistar rat. Taylor and Francis, London

    Google Scholar 

  53. Bermudez MA, Vicente AF, Romero MC et al (2011) Time course of cold cataract development in anesthetized mice. Curr Eye Res 36:278–284

    PubMed  CAS  Google Scholar 

  54. Delaye M, Clark JI, Benedek GB (1982) Identification of the scattering elements responsible for lens opacification in cold cataracts. Biophys J 37:647–656

    PubMed  CAS  Google Scholar 

  55. Carlton WW, Render JA (1991) Calcification of the cornea. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals: eye and ear. Springer, Berlin

    Google Scholar 

  56. Fabian RJ, Bond JM, Drobeck HP (1967) Induced corneal opacities in the rat. Br J Ophthalmol 51:124–129

    PubMed  CAS  Google Scholar 

  57. Losco PE, Troup CM (1988) Corneal dystrophy in Fischer 344 rats. Lab Anim Sci 38:702–710

    PubMed  CAS  Google Scholar 

  58. Mittl R, Galin MA, Opperman W (1970) Corneal calcification in spontaneously diabetic mice. Invest Ophthalmol 9:137–145

    PubMed  CAS  Google Scholar 

  59. Van Winkle TJ, Balk MW (1986) Spontaneous corneal opacities in laboratory mice. Lab Anim Sci 36:248–255

    PubMed  Google Scholar 

  60. Fortune B, Wang L, Bui BV et al (2005) Idiopathic bilateral optic nerve atrophy in rhesus macaque. Invest Ophthalmol Vis Sci 46:3943–3956

    PubMed  Google Scholar 

  61. Chiou GCY (1992) Ophthalmic toxicology. Raven, New York

    Google Scholar 

  62. Davidson SI, Rennie IG (1986) Ocular toxicity from systemic drug therapy. An overview of clinically important adverse reactions. Med Toxicol 1:217–224

    PubMed  CAS  Google Scholar 

  63. Grant WM (1986) Toxicology of the eye, 3rd edn. Charles C. Thomas, Springfield

    Google Scholar 

  64. Heywood R (1982) Histopathological and laboratory assessment of visual dysfunction. Environ Health Perspect 44:35–45

    PubMed  CAS  Google Scholar 

  65. Hockwin O, Green K, Rubin LF (1992) Manual of oculotoxicity testing of drugs. Gustav Fischer, Stuttgart

    Google Scholar 

  66. Lüllmann H, Lüllmann-Rauch R (1981) Tamoxifen-induced generalized lipidosis in rats subchronically treated with high doses. Toxicol Appl Pharmacol 61:138–146

    PubMed  Google Scholar 

  67. Massa T, Davis GJ, Schiavo D et al (1984) Tapetal changes in beagle dogs: II. Ocular changes after intravenous administration of a macrolide antibiotic—rosaramicin. Toxicol Appl Pharmacol 72:195–200

    PubMed  CAS  Google Scholar 

  68. Santaella RM, Fraunfelder FW (2007) Ocular adverse effects associated with systemic medications: recognition and management. Drugs 67:75–93

    PubMed  CAS  Google Scholar 

  69. Dillberger JE, Peiffer RL, Dykstra MJ et al (1996) The experimental antipsychotic agent 1192U90 targets tapetum lucidum in canine eyes. Toxicol Pathol 24:595–601

    PubMed  CAS  Google Scholar 

  70. Schiavo DM, Green JD, Traina VM, Spaet R, Zaidi I (1988) Tapetal changes in beagle dogs following oral administration of CGS 14796C, a potential aromatase inhibitor. Fund Appl Toxicol 10:329–334

    CAS  Google Scholar 

  71. Lai YL (1980) Outward movement of photoreceptor cells in normal rat retina. Invest Ophthalmol Vis Sci 19:849–856

    PubMed  CAS  Google Scholar 

  72. Lai YL, Masuda K, Mangum MD et al (1982) Subretinal displacement of photoreceptor nuclei in human retina. Exp Eye Res 34:219–228

    PubMed  CAS  Google Scholar 

  73. Fraunfelder FW (2003) Ocular adverse drug reactions. Exp Opin Drug Safety 2:411–420

    CAS  Google Scholar 

  74. Smith RS, Hawes NL, Miller J et al (2002) Photography and necropsy. In: Smith RS (ed) Systematic evaluation of the mouse eye: anatomy, pathology, and biomethods. CRC, Boca Raton, FL

    Google Scholar 

  75. Fix AS, Garman RH (2000) Practical aspects of neuropathology: a technical guide for working with the nervous system. Toxicol Pathol 28:122–131

    PubMed  CAS  Google Scholar 

  76. Thompson SW, Luna LG (1978) An atlas of artifacts encountered in the preparation of microscopic tissue sections. Charles C. Thomas Pub, Springfield

    Google Scholar 

  77. Lee WR (2002) Ophthalmic histopathology. Springer, London

    Google Scholar 

  78. Smith RS, Zabeleta A, John et al (2002) General and special histopathology. In: Smith RS (ed) Systematic evaluation of the mouse eye: anatomy, pathology, and biomethods. CRC, Boca Raton, FL

    Google Scholar 

  79. Dubielzig RR, Ketring KL, McLellan GJ et al (2010) The principles and practice of ocular pathology. Saunders, New York

    Google Scholar 

  80. Saby JA, Sigler RE, Klaus S (1991) Comparison of fixatives for histologic evaluation of the canine eye. J Histotechnol 14:251–255

    Google Scholar 

  81. Luna LG (1968) Manual of histology staining methods of the armed forces institute of pathology. McGraw-Hill Book Co, New York

    Google Scholar 

  82. Latendresse JR, Warbrittion AR, Jonassen H et al (2002) Fixation of testes and eyes using a modified Davidson’s fluid: comparison with Bouin’s fluid and conventional Davidson’s fluid. Toxicol Pathol 30:524–533

    PubMed  Google Scholar 

  83. Humason GL (1979) Histochemistry and special procedures. Animal tissue techniques. Freeman, San Francisco

    Google Scholar 

  84. Menocal NG, Ventura DB, Yanoff M (1980) Eye techniques. In: Sheehan DC, Hrapchak BB (eds) Routine processing of ophthalmic tissue for light microscopy. The CV Mosby Company, St. Louis, MO

    Google Scholar 

  85. Yanoff M, Fine BS (1967) Glutaraldehyde fixation of routine surgical eye tissue. Am J Ophthalmol 63:137–140

    PubMed  CAS  Google Scholar 

  86. Margo CE, Lee A (1995) Fixation of whole eyes: the role of fixative osmolarity in the production of tissue artifact. Graefe’s Arch Clin Exp Ophthalmol 233:366–370

    CAS  Google Scholar 

  87. Michon JJ, Li Z, Shioura N et al (1991) A comparative study of methods of photoreceptor morphometry. Invest Ophthalmol Vis Sci 32:280–284

    PubMed  CAS  Google Scholar 

  88. Mecklenburg L, Schraermeyer U (2007) An overview on the toxic morphological changes in the retinal pigment epithelium after systemic compound administration. Toxicol Pathol 35:252–267

    PubMed  CAS  Google Scholar 

  89. Prophet EB (1992) AFIP laboratory methods in histotechnology. American Registry of Pathology, Washington, DC

    Google Scholar 

  90. Giordano C, Weigt A, Vercelli A et al (2005) Immunohistochemical identification of Encephalitozoon cuniculi in phacoclastic uveitis in four rabbits. Vet Ophthalmol 8:271–275

    PubMed  CAS  Google Scholar 

  91. Labelle P, Reilly CM, Naydan DK, Labelle LA (2012) Immunohistochemical characteristics of normal canine eyes. Vet Pathol 49:860–869

    PubMed  CAS  Google Scholar 

  92. Dubielzig RR, Steinberg H, Garvin H et al (1998) Iridociliary epithelial tumors in 100 dogs and 17 cats: a morphological study. Vet Ophthalmol 1:223–231

    PubMed  Google Scholar 

  93. Walker RA (2006) Quantification of immunohistochemistry—issues concerning methods, utility and semiquantitative assessment I. Histopathology 49:406–410

    PubMed  CAS  Google Scholar 

  94. Eagle RC (2008) Immunohistochemistry in diagnostic ophthalmic pathology: a review. Clin Experiment Ophthalmol 36:675–688

    PubMed  Google Scholar 

  95. Dabbs DJ (2002) Diagnostic immunohistochemistry. Churchill Livingstone, London

    Google Scholar 

  96. Ramos-Vara JA (2005) Technical aspects of immunohistochemistry. Vet Pathol 42:405–426

    PubMed  CAS  Google Scholar 

  97. Webster JD, Miller MA, DuSold D, Ramos-Vara J (2009) Effects of prolonged formalin fixation on diagnostic immunohistochemistry in domestic animals. J Histochem Cytochem 57:753–761

    PubMed  CAS  Google Scholar 

  98. Berod A, Hartman BK, Pujol JF (1981) Importance of fixation in immunohistochemistry: use of formaldehyde solutions at variable pH for the localization of tyrosine hydroxylase. J Histochem Cytochem 29:844–850

    PubMed  CAS  Google Scholar 

  99. McKay JS, Steele SJ, Ahmed G et al (2009) An antibody panel for immunohistochemical analysis of the retina in Davidson’s-fixed, paraffin-embedded eyes of rats. Exp Toxicol Pathol 61:91–100

    PubMed  CAS  Google Scholar 

  100. Ramos-Vara JA, Beissenherz M (2000) Optimization of immunohistochemical methods using two different AR methods on formalin-fixed, paraffin-embedded tissues: experience with 63 markers. J Vet Diagn Invest 12:307–311

    PubMed  CAS  Google Scholar 

  101. Shi SR, Key ME, Kalra KL (1991) Antigen retrieval in formalin-fixed, paraffin-embedded tissue: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39:741–748

    PubMed  CAS  Google Scholar 

  102. Polak JM, Van Noorden S (2003) Introduction to immunocytochemistry. Bios Scientific Publishers Ltd, Oxford

    Google Scholar 

  103. Petrosyan K, Tamayo R, Joseph D (2002) Sensitivity of a novel biotin-free detection reagent (Powervision™) for immunohistochemistry. J Histotechnol 25:247–250

    CAS  Google Scholar 

  104. Sabattini E, Bisgaard K, Ascani S et al (1998) The EnVision™ system: a new immunohistochemical method for diagnostics and research: critical comparison with the APAAP, ChemMateTM CSA, LABC, and SABC techniques. J Clin Pathol 51:506–511

    PubMed  CAS  Google Scholar 

  105. Bancroft JD, Gamble M (2002) Theory and practice of histological techniques. Churchill Livingstone, London

    Google Scholar 

  106. Nalbandian RM, Nagy DW, Vassallo JM (1990) Artifact-free ocular sections: a controlled comparison study between paraffin and glycol methacrylate techniques. J Histotechnol 13:35–41

    Google Scholar 

  107. Fagerland JA, Wall HG, Pandher K et al (2012) Ultrastructural analysis in preclinical safety evaluation. Toxicol Pathol 40:391–402

    PubMed  Google Scholar 

  108. Zaki FG, Keysser CH (1973) Application of electron microscopy to drug safety evaluation. Toxicol Pathol 1(4):4–5

    Google Scholar 

  109. Hayat MA (2000) Principles and techniques of electron microscopy: biological applications. Cambridge University Press, Cambridge

    Google Scholar 

  110. Sadun AA, Smith LE, Kenyon KR (1983) Paraphenylenediamine: a new method for tracing human visual pathways. J Neuropathol Exp Neurol 42:200–206

    PubMed  CAS  Google Scholar 

  111. Dykstra MJ, Reuss LE (2003) Biological electron microscopy: theory, techniques and troubleshooting. Kluwer, New York

    Google Scholar 

  112. Dykstra MJ, Mann PJ, Elwell MR et al (2002) Suggested standard operating procedures (SOPs) for the preparation of electron microscopy samples of toxicology/pathology samples for toxicology/pathology studies in a GLP environment. Toxicol Pathol 30:735–743

    PubMed  CAS  Google Scholar 

  113. Braet F, De Zanger R, Wisse E (1997) Drying cells for SEM, AFM and TEM by hexamethyldisilazane: a study on hepatic endothelial cells. J Microsc 186:84–87

    PubMed  CAS  Google Scholar 

  114. Bozzola JJ, Russell LD (1999) Electron microscopy: principles and techniques for biologists, 2nd edn. Jones and Bartlett, Sudbury

    Google Scholar 

  115. Glauert AM, Lewis PR (1998) Biological specimen preparation for transmission electron microscopy. Princeton University Press, Princeton, NJ

    Google Scholar 

  116. Wolf T (2011) Preparation of drosophila eye specimens for scanning electron microscopy. Cold Spring Harbor Protoc 2011(11):1383–1385. doi:10.1101/pdb.prot066506

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this protocol

Cite this protocol

Teixeira, L.B.C., Render, J.A. (2013). Methodologies for Microscopic Characterization of Ocular Toxicity. In: Gilger, B. (eds) Ocular Pharmacology and Toxicology. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/7653_2013_5

Download citation

  • DOI: https://doi.org/10.1007/7653_2013_5

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-744-0

  • Online ISBN: 978-1-62703-745-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics