This Event is licensed under the Creative Commons BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.
Event: 1877
Key Event Title
Altered, retinal layer structure
Short name
Biological Context
Level of Biological Organization |
---|
Tissue |
Organ term
Organ term |
---|
eye |
Key Event Components
Process | Object | Action |
---|---|---|
retina layer formation | retina | morphological change |
Key Event Overview
AOPs Including This Key Event
AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|
TPOi retinal layer structure | KeyEvent | Allie Always (send email) | Open for citation & comment | Under Review |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
zebrafish | Danio rerio | High | NCBI |
Life Stages
Life stage | Evidence |
---|---|
Embryo | High |
Larvae | High |
Sex Applicability
Term | Evidence |
---|---|
Unspecific | Moderate |
Key Event Description
The anatomy and histology of the eye are highly conserved among vertebrates. The cornea and lens refract and focus light onto the posterior chamber of the eye, the vitreous cavity, which is covered by the retina. The retina consists of three specialised layers of cells, the outermost of which is formed by photoreceptors that absorb light and transmit the subsequent neural signal to the innermost layers, which consist of neurons specialised in processing and transmitting this neural signal (Wässle and Riemann, 1978; Cameron and Carney, 2000 ; Rockhill et al, 2000; Fadool, 2003). The neurons of the innermost layer converge to form the optic nerve, which transmits visual information to the brain (Gestri et al., 2012). The retina has different types of photoreceptors, the cones, which are responsible for colour vision, and the rods, which enable vision in the dark or in very low light conditions. In adults, cones are distributed in the retina in a precise and very regular arrangement, forming a photoreceptor mosaic. The precise spatiotemporal pattern of maturation of cones may affect the organization of this mosaic, and THs appear to play a role in the coordination of this maturation process (Suzuki et al., 2013). In the fish retina, this arrangement is most evident in the outer nuclear layer where the position of each cone subtype is precisely arranged relative to the others (Fadool, 2003; Robinson et al., 1993) resulting in a highly ordered crystalline-like mosaic.
The retinal pigment epithelium (RPE) is important to maintain a healthy and functional retina (Strauss 2005). The strong connection between the RPE cells with the tight junction, creates a blood-retinal barrier to mediate the directional transport of ions, water and nutrients while removing waste products. Another key function of the RPE is to absorb excess light energy to protect the neural retina from phototoxicity (Plafker 2012). Phagocytosis of spilled photoreceptor outer segments (Lister 2002) is another function of the RPE to maintain balanced photoreceptor growth, which is important for their physiological function.
Studies that detect and measure altered retinal layer structure after exposure to THs or endocrine disruptors show, for example, altered cone cell number (Allison et al., 2006; Houbrechts et al., 2016; Vancamp et al., 2019), altered retinal cell number (Dong et al., 2014), or a general alteration of retinal morphology (Gamborino et al., 2001; Houbrechts et al., 2016; Komoike et al., 2013; Li et al., 2012; Reider & Connaughton, 2014), alteration of the RPE (Baumann et al., 2016), abnormal cone differentiation (Duval & Allison, 2018; Suzuki et al., 2013; Viets et al., 2016) or prevention of the opsin switch (Gan & Flamarique, 2010; Raine & Hawryshyn, 2009). Especially the TH receptor TRβ seems to be a key regulator by determining the expression of photoreceptor development in the retina (Ng et al., 2010; Suzuki et al., 2013; Deveau et al., 2019, 2020).
How It Is Measured or Detected
For assessment of eye structure and layers, mostly simple morphometric analyses based on histological sections are sufficient. This can either be electron microscopy for subcellular changes, or normal light microscopy for cellular changes. Specific antibody staining might help to identify the different retinal layers and photoreceptor types, but usually, they are easily distinguishable by normal histological staining (e.g. HE staining).
Measurement of cell layer diameter is the most popular and simple method to assess changes in eye structure and layers. Moreover, measurement of the pigmentation grade of the retinal pigment epithelium can be used to assess structural changes. Moreover, semi-quantitative assessment of severity grades of morphological changes can be assessed.
(reviewed in Chen 2020)
Domain of Applicability
Taxonomic applicability: In general, the eye structure is very conserved among vertebrates, but some differences exist with regard to shape and expression of the different retinal layers. Fig. 1 (from Richardson 2012) demonstrates the histology of the human vs the zebrafish eye. As in humans, the mature zebrafish retina consists of three nuclear layers separated by two plexiform layers. The photoreceptor rod and cone nuclei are located in the outer nuclear layer; the amacrine, horizontal, and Müller glial cell bodies are found in the inner nuclear layer and the ganglion cell bodies are placed in the ganglion cell layer. The plexiform layers connect these layers. In contrast to zebrafish, the human retina lacks UV-sensitive cones.
Other structural differences between species are mostly related to their lifestyle (e.g. nocturnal vs diurnal) (Bibliowicz 2011) and cannot be generalized for specific vertebrate classes.
Life-stage applicability: Eye structure differs between life stages, as the different retinal layers do not develop at the same time and the eye itself grows with the organism. Eye development in zebrafish closely resembles the one in humans and other vertebrates. The eye develops from three different embryological tissues that form the specific structures of the eye, starting with the optic vesicle at 16 hpf, which further develops into the two-layered optic cup composed of the retinal neuroepithelium and pigmented epithelium until 20 hpf. Lens development begins as a lens placode that forms a solid lens mass by 22 hpf. Afterwards, the neuroectodermal layers of the optic vesicle invaginate ventrally by 24 hpf. By 48 hpf, zebrafish eye morphogenesis is almost complete with only retinal neurogenesis continuing. Retinal pigment epithelium flattening and final differentiation occurs around 27 hpf (Moreno-Marmol and others 2018). By 60 hpf, the different layers of the retina can be distinguished (Morris and Fadool 2005; Schmitt and Dowling 1999). Thereafter, further differentiation and maturation of the layers and cell types continues (Raymond and others 1995). For example, rods continue to mature until around 20 dpf (Morris and Fadool 2005). Impacts on retinal layer structure have been reported at 48, 66, 72, 96 and 120 hpf during zebrafish embryo-eleutheroembryo development (Baumann and others 2016; Komoike and others 2013; Reider and Connaughton 2014). Since the term 'eleutheroembryo' (stage starting at hatching and ending with free-feeding) is not available, the terms 'embryo' and 'larvae' were selected to reflect this.
Sex applicability: Zebrafish are undifferentiated gonochorists since both sexes initially develop an immature ovary (Maack and Segner, 2003). Immature ovary development progresses until approximately the onset of the third week. Later, in female fish immature ovaries continue to develop further, while male fish undergo transformation of ovaries into testes. Final transformation into testes varies among male individuals, however finishes usually around 6 weeks post fertilization. Effects on retinal layers during early development are therefore expected to be independent of sex.
At later life stages, however, sex dependency cannot be excluded. Sexual dimorphism of eye sclera surface exposure has been recently discovered (Danel et al. 2018; Danel et al., 2020). Danel et al. (2020) also found that women have rounder eye fissures and brighter irises compared to men. Maekawa et al. (2010) observed eye abnormalities such as microphthalmia and cataract in female mice but not in male mice when the fatty acid composition of the diet was changed during gestation. The authors hypothesized that this was due to differences in lipid metabolism. This suggests that effects of other factors on eye structure could also be sex- dependent in vertebrates.
Evidence for perturbation by stressor: Multiple studies demonstrate that eye development and its resulting structure can be disrupted by different stressors (reviewed for example by Chen 2020).
References
Allison, W. T., Dann, S. G., Veldhoen, K. M., & Hawryshyn, C. W. (2006). Degeneration and regeneration of ultraviolet cone photoreceptors during development in rainbow trout. Journal of Comparative Neurology, 499(5), 702–715. https://doi.org/10.1002/cne.21164
Ali S, Champagne DL, Richardson MK. Behavioral profiling of zebrafish embryos exposed to a panel of 60 water-soluble compounds. Behav Brain Res. 2012;228(2):272-283. doi:10.1016/j.bbr.2011.11.020
Baumann, L., Ros, A., Rehberger, K., Neuhauss, S. C. F., & Segner, H. (2016). Thyroid disruption in zebrafish (Danio rerio) larvae: Different molecular response patterns lead to impaired eye development and visual functions.Aquatic Toxicology, 172, 44–55. https://doi.org/10.1016/j.aquatox.2015.12.015
Baumann, L., Segner, H., Ros, A., Knapen, D., & Vergauwen, L. (2019). Thyroid Hormone Disruptors Interfere with Molecular Pathways of Eye Development and Function in Zebrafish. International Journal of Molecular Sciences, 20(7), 1543. https://doi.org/10.3390/ijms20071543
Bibliowicz J, Tittle RK, Gross JM. Toward a Better Understanding of Human Eye Disease: Insights from the Zebrafish, Danio Rerio. Vol 100.; 2011. doi:10.1016/B978-0-12-384878-9.00007-8
Cameron, D.A., Carney, L.H., 2000. Cell mosaic patterns in the native and regenerated inner retina of zebrafish: implications for retinal assembly. J. Comp. Neurol. 416, 356–367.
Danel DP, Wacewicz S, Kleisner K, Lewandowski Z, Kret ME, Zywiczynski P, Perea-Garcia JO. 2020. Sex differences in ocular morphology in Caucasian people: a dubious role of sexual selection in the evolution of sexual dimorphism of the human eye. Behavioral Ecology and Sociobiology 74(10).
Danel DP, Wacewicz S, Lewandowski Z, Zywiczynski P, Perea-Garcia JO. 2018. Humans do not perceive conspecifics with a greater exposed sclera as more trustworthy: a preliminary cross-ethnic study of the function of the overexposed human sclera. Acta Ethologica 21(3):203-208.
Dong, W., Macaulay, L. J., Kwok, K. W., Hinton, D. E., Ferguson, P. L., & Stapleton, H. M. (2014). The PBDE metabolite 6-OH-BDE 47 affects melanin pigmentation and THRβMRNA expression in the eye of zebrafish embryos. Endocrine Disruptors, 2(1), e969072. https://doi.org/10.4161/23273739.2014.969072
Duval, M. G., & Allison, W. T. (2018). Photoreceptor progenitors depend upon coordination of gdf6a, thrβ, and tbx2b to generate precise populations of cone photoreceptor subtypes. Investigative Ophthalmology and Visual Science, 59(15), 6089–6101. https://doi.org/10.1167/iovs.18-24461
Fadool, J.M., 2003. Development of a rod photoreceptor mosaic revealed in transgenic zebrafish. Dev. Biol. 258, 277–290.
Gamborino, M. J., Sevilla-Romero, E., Muñoz, A., Hernández-Yago, J., Renau-Piqueras, J., & Pinazo-Durán, M. D. (2001). Role of thyroid hormone in craniofacial and eye development using a rat model. Ophthalmic Research,33(5), 283–291. https://doi.org/10.1159/000055682
Gan, K. J., & Flamarique, I. N. (2010). Thyroid hormone accelerates opsin expression during early photoreceptor differentiation and induces opsin switching in differentiated TRα-expressing cones of the salmonid retina. Developmental Dynamics, 239(10), 2700–2713. https://doi.org/10.1002/dvdy.22392
Gestri, G., Link, B. A., & Neuhauss, S. C. (2012). The visual system of zebrafish and its use to model
Houbrechts, A. M., Vergauwen, L., Bagci, E., Van houcke, J., Heijlen, M., Kulemeka, B., Hyde, D. R., Knapen, D., & Darras, V. M. (2016). Deiodinase knockdown affects zebrafish eye development at the level of gene expression, morphology and function. Molecular and Cellular Endocrinology, 424, 81–93. https://doi.org/10.1016/j.mce.2016.01.018
Komoike, Y., Matsuoka, M., & Kosaki, K. (2013). Potential teratogenicity of methimazole: Exposure of zebrafish embryos to methimazole causes similar developmental anomalies to human methimazole embryopathy. Birth Defects Research Part B - Developmental and Reproductive Toxicology, 98(3), 222–229. https://doi.org/10.1002/bdrb.21057
Li, Z., Ptak, D., Zhang, L., Walls, E. K., Zhong, W., & Leung, Y. F. (2012). Phenylthiourea specifically reduces zebrafish eye size. PLoS ONE,7(6), 1–14. https://doi.org/10.1371/journal.pone.0040132
Lister JA. Development of pigment cells in the zebrafish embryo. Microsc Res Tech. 2002;58(6):435-441. doi:10.1002/jemt.10161
Moreno-Marmol T, Cavodeassi F, Bovolenta P. 2018. Setting Eyes on the Retinal Pigment Epithelium. Frontiers in Cell and Developmental Biology 6.
Morris AC, Fadool JM. 2005. Studying rod photoreceptor development in zebrafish. Physiology & Behavior 86(3):306-313.
Plafker SM, O'Mealey GB, Szweda LI. Mechanisms for countering oxidative stress and damage in retinal pigment epithelium. Int Rev Cell Mol Biol. 2012;298:135-77. doi: 10.1016/B978-0-12-394309-5.00004-3. PMID: 22878106; PMCID: PMC3564215.
Raine, J. C., & Hawryshyn, C. W. (2009). Changes in thyroid hormone reception precede SWS1 opsin downregulation in trout retina. Journal of Experimental Biology, 212(17), 2781–2786. https://doi.org/10.1242/jeb.030866
Raymond PA, Barthel LK, Curran GA. 1995. DEVELOPMENTAL PATTERNING OF ROD AND CONE PHOTORECEPTORS IN EMBRYONIC ZEBRAFISH. Journal of Comparative Neurology 359(4):537-550.
Reider, M., & Connaughton, V. P. (2014). Effects of low-dose embryonic thyroid disruption and rearing temperature on the development of the eye and retina in zebrafish. Birth Defects Research. Part B, Developmental and Reproductive Toxicology, 101(5), 347–354. https://doi.org/10.1002/bdrb.21118
Rockhill, R.L., Euler, T., Masland, R.H., 2000. Spatial order within but not between types of retinal neurons. Proc. Natl. Acad. Sci. USA 97, 2303–2307.
Schmitt EA, Dowling JE. 1999. Early retinal development in the zebrafish, Danio rerio: Light and electron microscopic analyses. Journal of Comparative Neurology 404(4):515-536.
Suzuki, S. C., Bleckert, A., Williams, P. R., Takechi, M., Kawamura, S., & Wong, R. O. L. (2013). Cone photoreceptor types in zebrafish are generated by symmetric terminal divisions of dedicated precursors. Proceedings of the National Academy of Sciences, 110(37), 15109 LP – 15114.https://doi.org/10.1073/pnas.1303551110
Strauss O. The retinal pigment epithelium in visual function. Physiol Rev. 2005 Jul;85(3):845-81. doi: 10.1152/physrev.00021.2004. PMID: 15987797.
Vancamp, P., Bourgeois, N. M. A., Houbrechts, A. M., & Darras, V. M. (2019). Knockdown of the thyroid hormone transporter MCT8 in chicken retinal precursor cells hampers early retinal development and results in a shift towards more UV/blue cones at the expense of green/red cones. Experimental Eye Research, 178(September 2018), 135–147. https://doi.org/10.1016/j.exer.2018.09.018
Viets, K., Eldred, K. C., & Johnston, R. J. (2016). Mechanisms of Photoreceptor Patterning in Vertebrates and Invertebrates. Trends in Genetics, 32(10), 638–659. https://doi.org/10.1016/j.tig.2016.07.004
Wässle, H., Riemann, H.J., 1978. The mosaic of nerve cells in the mammalian retina. Proc. R. Soc. London B Biol. Sci. 200, 441–461.