Scientific and Regulatory Policy Committee Points to Consider: Fixation, Trimming, and Sectioning of Nonrodent Eyes and Ocular Tissues for Examination in Ocular and General Toxicity Studies

1. Nork, TM, Rasmussen, CA, Christian, BJ, Croft, MA, Murphy, CJ. Emerging imaging technologies for assessing ocular toxicity in laboratory animals. In: Weir, A, Collins, M, eds. Assessing Ocular Toxicology in Laboratory Animals. Molecular and Integrative Toxicology. Humana Press; 2012:53–121.
Google Scholar | Crossref2. Ramos, MF, Attar, M, Stern, M, et al. Safety evaluation of ocular drugs. In: Faqi, AS , ed. A Comprehensive Guide to Toxicology in Preclinical Drug Development. 2nd ed. Elsevier; 2017:758–812.
Google Scholar | Crossref3. Soukup, P, Lenz, B, Altmann, B, Badillo, S, Atzpodien, E-A, Pot, SA. Combined cSLO-OCT imaging as a tool in preclinical ocular toxicity testing: a comparison to standard in-vivo and pathology methods. J Pharmacol Toxicol Methods. 2020;104:106873.
Google Scholar | Crossref | Medline4. Yiu, G, Wang, Z, Munevar, C, et al. Comparison of chorioretinal layers in rhesus macaques using spectral-domain optical coherence tomography and high-resolution histological sections. Exp Eye Res. 2018;168:69–76.
Google Scholar | Crossref | Medline5. Short, B . Selected aspects of ocular toxicity studies with a focus on high-quality pathology reports: a pathology/toxicology consultant’s perspective. Toxicol Pathol. Preprint. Posted online August 20, 2020. doi:10.1177/0192623320946712.
Google Scholar6. Kolb, H . Photoreceptors. Webvision. Moran Eye Center. Updated July 2013. Accessed September 21, 2021. https://webvision.med.utah.edu/book/part-ii-anatomy-and-physiology-of-the-retina/photoreceptors/
Google Scholar7. Imamoto, Y, Shichida, Y. Cone visual pigments. Biochim Biophys Acta. 2014;1837(5):664–673.
Google Scholar | Crossref | Medline8. Shichida, Y, Matsuyama, T. Evolution of opsins and phototransduction. Phil Trans R Soc B. 2009;364:2881–2895.
Google Scholar | Crossref | Medline9. May-Simera, H, Nagel-Wolfrum, K, Wolfrum, U. Cilia—the sensory antennae in the eye. Prog Retin Eye Res. 2017;60:144–180.
Google Scholar | Crossref | Medline10. Muthuswamy, A, Pardo, ID, Rao, DB, Switzer, RC, III, Sharma, AK, Bolon, B. Neuroanatomy and sampling of central projections for the visual system in mammals used in toxicity testing. Toxicol Pathol. 2020;26:192623320967279. doi:10.1177/0192623320967279.
Google Scholar11. Lamb, TD . Why rods and cones? Eye (Lond). 2016;30(2):179–185.
Google Scholar | Crossref | Medline12. Beauchemin, ML . The fine structure of the pig’s retina. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1974;190(1):27–45.
Google Scholar | Crossref | Medline13. Chandler, MJ, Smith, PJ, Samuelson, DA, MacKay, EO. Photoreceptor density of the domestic pig retina. Vet Ophthalmol. 1999;2(3):179–184.
Google Scholar | Crossref | Medline14. Curcio, CA, Sloan, KR, Kalina, RE, Hendrickson, AE. Human photoreceptor topography. J Comp Neurol. 1990;292(4):497–523.
Google Scholar | Crossref | Medline15. Famiglietti, EV, Sharpe, SJ. Regional topography of rod and immunocytochemically characterized “blue” and “green” cone photoreceptors in rabbit retina. Vis Neurosci. 1995;12(6):1151–75.
Google Scholar | Crossref | Medline16. Gerke, CG, Hao, F, Wong, F. Topography of rods and cones in the retina of the domestic pig. HKMJ. 1995;1(4):302–308.
Google Scholar17. Packer, O, Hendrickson, AE, Curcio, CA. Photoreceptor topography of the retina in the adult pigtail macaque (Macaca nemestrina). J Comp Neurol. 1989;288(1):165–83.
Google Scholar | Crossref | Medline18. Wikler, KC, Williams, RW, Rakic, P. Photoreceptor mosaic: number and distribution of rods and cones in the rhesus monkey retina. J Comp Neurol. 1990;297(4):499–508.
Google Scholar | Crossref | Medline19. Ahnelt, PK, Kolb, H. The mammalian photoreceptor mosaic-adaptive design. Prog Retin Eye Res. 2000;19(6):711–77. doi:10.1016/s1350-9462(00)00012-4. PMID: 11029553.
Google Scholar | Crossref | Medline20. Bernstein, PS, Li, B, Vachali, PP, et al. Lutein, zeaxanthin, and meso-zeaxanthin: the basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease. Prog Retin Eye Res. 2016;50:34–66.
Google Scholar | Crossref | Medline21. Bringmann, A, Syrbe, S, Görner, K, et al. The primate fovea: structure, function and development. Prog Retin Eye Res. 2018;66:49–84.
Google Scholar | Crossref | Medline22. Hendrickson, A, Kupfer, C. The histogenesis of the fovea in the macaque monkey. Invest Opthalmol Vis Sci. 1976;15(9):746–756.
Google Scholar | Medline23. Vezina, M . Comparative ocular anatomy in commonly used laboratory animals. In: Weir, A, Collins, M, eds. Assessing Ocular Toxicology in Laboratory Animals. Molecular and Integrative Toxicology. Humana Press; 2012:1–21.
Google Scholar | Crossref24. Oyster, CW, Takahashi, ES, Hurst, DC. Density, soma size, and regional distribution of rabbit retinal ganglion cells. J Neurosci. 1981;1(12):1331–1346.
Google Scholar | Crossref | Medline25. Mowat, FM, Petersen-Jones, SM, Williamson, H, et al. Topographical characterization of cone photoreceptors and the area centralis of the canine retina. Mol Vis. 2008;14:2518–2527.
Google Scholar | Medline26. Yamaue, Y, Hosaka, YZ, Ueharai, M. Spatial relationships among the cellular tapetum, visual streak and rod density in dogs. J Vet Med Sci. 2015;77(2):175–179.
Google Scholar | Crossref | Medline27. Shrader, SM, Greentree, WF. Göttingen minipigs in ocular research. Toxicol Pathol. 2018;46(4):403–407.
Google Scholar | SAGE Journals | ISI28. Beltran, WA, Cideciyan, AV, Guziewicz, KE, et al. Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations. PLoS One. 2014;9(3):e90390. doi: 10.1371/journal.pone.0090390.
Google Scholar | Crossref | Medline29. Peichl, L . Topography of ganglion cells in the dog and wolf retina. J Comp Neurol. 1992;324(4):603–620.
Google Scholar | Crossref | Medline30. De Schaepdrijver, L, Simoens, P, Lauwers, H, De Geest, JP. Retinal vascular patterns in domestic animals. Res Vet Sci. 1989;47(1):34–42.
Google Scholar | Crossref | Medline31. Muraoka, Y, Ikeda, HO, Nakano, N, et al. Real-time imaging of rabbit retina with retinal degeneration by using spectral-domain optical coherence tomography. PLoS One. 2012;7(4):e36135. doi:10.1371/journal.pone.0036135.
Google Scholar | Crossref | Medline32. Hendrickson, A, Hicks, D. Distribution and density of medium- and short-wavelength selective cones in the domestic pig retina. Exp Eye Res. 2002;74(4):435–444.
Google Scholar | Crossref | Medline33. Vrolyk, V, Desmarais, MJ, Lambert, D, Haruna, J, Benoit-Biancamano, MO. Neonatal and juvenile ocular development in Göttingen minipigs and domestic pigs: a histomorphological and immunohistochemical study. Vet Pathol. 2020;57(6):889–914.
Google Scholar | SAGE Journals | ISI34. Scott, P, de Castro, J, DeMarco, P, et al. Progression of Pro23His retinopathy in a miniature swine model of retinitis pigmentosa. Transl Vis Sci Technol. 2017;6(2):4.
Google Scholar | Crossref | Medline35. Volland, S, Esteve-Rudd, J, Hoo, J, Yee, C, Williams, DS. A comparison of some organizational characteristics of the mouse central retina and the human macula. PLoS One. 2015;10(4):e0125631. Published April 29, 2015. doi:10.1371/journal.pone.0125631.
Google Scholar | Crossref | Medline36. Rodger, J, Dunlop, SA, Beaver, R, Beazley, LD. The development and mature organization of the end-artery retinal vasculature in a marsupial, the dunnart Sminthopsis crassicaudata. Vis Res. 2001;41(1):13–21.
Google Scholar | Crossref | Medline37. Simoens, P, De Schaepdrijver, L, Lauwers, H. Morphologic and clinical study of the retinal circulation in the miniature pig. A: morphology of the retinal microvasculature. Exp Eye Res. 1992;54(6):965–973.
Google Scholar | Crossref | Medline38. Peynshaert, K, Devoldere, J, Minnaert, A-K, De Smedt, SC, Remaut, K. Morphology and composition of the inner limiting membrane: species-specific variations and relevance toward drug delivery research. Curr Eye Res. 2019;44(5):465–475.
Google Scholar | Crossref | Medline39. Lee, MS, Gupta, N, Loewenstein, J, Wepner, M, Milam, AM. Retinal cone toxicity in an ovarian cancer patient treated with Irofluven. IOVS. 2003;44:13, 519.
Google Scholar40. Vellonen, KS, Soini, EM, del Amo, EM, Urtti, A. Prediction of ocular drug distribution from systemic blood circulation. Mol Pharmaceutics. 2016;13(9):2906–2911.
Google Scholar | Crossref | Medline41. Bregman, CL, Adler, RR, Morton, DG, Regan, KS, Yano, BL. Recommended tissue list for histopathologic examination in repeat-dose toxicity and carcinogenicity studies: a proposal of the Society of Toxicologic Pathology (STP). Toxicol Pathol. 2003;31(2):252–253.
Google Scholar | SAGE Journals | ISI42. Bolon, B, Garman, RH, Pardo, ID, et al. STP position paper: recommended practices for sampling and processing the nervous system (brain, spinal cord, nerve, and eye) during nonclinical general toxicity studies. Toxicol Pathol. 2013;41(7):1028–1048.
Google Scholar | SAGE Journals | ISI43. Naylor, SW, Czajkowski, M, Harvey, W, Smith, M, Bradley, AE, Cary, M. Histopathological findings in cynomolgus macaques (Macaca fascicularis) consisted with secondary immunological reaction to biotherapeutics with an emphasis on the CNS and eye. Toxicol Pathol. 2019;47(2):165–173.
Google Scholar | SAGE Journals | ISI44. Ramos, MF, Teixeira, L, Brandt, CR, Auyeung-Kim, D. Ocular immunopathology. In: Parker, GA , ed. Immunopathology in Toxicology and Drug Development. Molecular and Integrative Toxicology, Volume 2, Organ Systems. Humana Press; 2017:695–762.
Google Scholar | Crossref45. Wessels, U, Zadak, M, Reiser, A, et al. Immunogenicity testing of therapeutic antibodies in ocular fluids after intravitreal injection. Bioanalysis. 2018;10(11):803–814.
Google Scholar | Crossref | Medline46. Lorget, F, Parenteau, A, Carrier, M, et al. Characterization of the pH and temperature in the rabbit, pig, and monkey eye: key parameters for the development of long-acting delivery ocular strategies. Mol Pharm. 2016;13(9):2891–2896.
Google Scholar | Crossref | Medline47. Sorden, SD, Larsen, T, McPherson, LE, Turner, OC, Carroll, EE, Sharma, AK. Spontaneous background and procedure-related microscopic findings and common artifacts in ocular tissues of laboratory animals in ocular studies. Toxicol Pathol. November 2020. doi:10.1177/0192623320966244.
Google Scholar48. Latendresse, JR, Warbrittion, AR, Jonassen, H, Creasy, DM. Fixation of testes and eyes using a modified Davidson’s fluid: comparison with Bouin’s fluid and conventional Davidson’s fluid. Toxicol Pathol. 2002;30(4):524–533.
Google Scholar | SAGE Journals | ISI49. Ramos, MF, Baker, J, Atzpodien, EA, et al. Nonproliferative and proliferative lesions of the rat and mouse special sense organs (ocular [eye and glands]), olfactory, and otic). Toxicol Pathol. 2018;31(3 suppl):97S–214 S.
Google Scholar | Crossref50. Schafer, K, Render, J. Toxicologic pathology of the eye: histologic preparation and alterations of the anterior segment. In: Weir, A, Collins, M, eds. Assessing Ocular Toxicology in Laboratory Animals. Molecular and Integrative Toxicology. Humana Press; 2012:159–217.
Google Scholar | Crossref51. Atzpodien, EA, Jacobsen, B, Funk, J, et al. Advanced clinical imaging and tissue-based biomarkers of the eye for toxicology studies in minipigs. Toxicol Pathol. 2016;44(3):398–413.
Google Scholar | SAGE Journals | ISI52. Chidlow, G, Daymon, M, Wood, JPM, Casson, RJ. Localization of a wide-ranging panel of antigens in the rat retina by immunohistochemistry: comparison of Davidson’s solution and formalin as fixatives. J Histochem Cytochem. 2011;59(10):884–898.
Google Scholar | SAGE Journals | ISI53. Stradleigh, TW, Ishida, AT. Fixation strategies for retinal immunohistochemistry. Prog Retin Eye Res. 2015;48:181–202.

Comments (0)

No login
gif