Vision - Retina Development

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Retina development (Week 8 stage 22)
Retina development (Week 8 stage 22)

Introduction

The retina and its development has been the subject of research from the early histology studies of Santiago Ramón y Cajal (1852 - 1934) and Camillo Golgi (1843 - 1926). It has a complex differentiation involving both a neural retina and a pigmented retina, in the embryo separated by a space and in the adult closely apposed to each other.

The retina is also a key focus of clinical research, as genetic or environmental damage and vision loss is generally a result of damage to the retinal cells or their processes. Retinitis pigments is a degenerative retinal disease. Retinoblastoma is retinal cancer that allowed researchers to identify retinoblastoma protein (Rb), the first identified tumour suppressor protein acting as a G1 cell cycle checkpoint.


Vision Links: vision | lens | retina | placode | extraocular muscle | cornea | eyelid | vision abnormalities | Student project 1 | Student project 2 | Category:Vision | sensory
Historic Embryology  
1906 Eye Embryology | 1907 Development Atlas | 1912 Eye Development | 1912 Nasolacrimal Duct | 1918 Grays Anatomy | 1921 Eye Development | 1922 Optic Primordia | 1925 Iris | 1927 Oculomotor | 1928 Human Retina | 1928 Retina | 1928 Hyaloid Canal | Historic Disclaimer

Some Recent Findings

  • Analysis of expression of transcription factors in early human retina[1] "Here, we analyze the expression of transcription factors that are involved in the early development of the retina in human embryos at 6-12 weeks post-conception. Our work demonstrates that early developing neural retinas can be divided into two layers, the outer and inner neuroblast layers. Eye-field transcription factors and those related to the early development of the retina have distinct expression patterns in the two layers. Cell-type-specific transcription factors emerge at 8 weeks. These data provide clear and systemic structures for early retinal development in human."
  • Development of Retinal Layers in Prenatal Human Retina[2] "A histology collection of human eyes from fetal week (Fwk) 8 to postnatal (P) 10 weeks was analyzed. The length of the nasal and temporal retina was measured along the horizontal meridian in 20 eyes. The location of the inner plexiform layer (IPL) and outer plexiform layer (OPL) was identified at each age, and its length measured. The human eye retinal length increased from 5.19 mm at Fwk 8 to 20.92 mm at midgestation to 32.88 mm just after birth. The IPL appeared in the presumptive fovea at Fwk 8, reached the eccentricity of the optic nerve by Fwk 12 and was present to both nasal and temporal peripheral edges by Fwk 18-21. By contrast, the OPL developed slowly. A short OPL was first present in the Fwk 11 fovea and did not reach the eccentricity of the optic nerve until midgestation. The OPL reached the retinal edges by Fwk 30. Laminar development of both IPL and OPL occurred before vascular formation In human fetal retina, the IPL reached the far peripheral edge of the retina by midgestation and the OPL by late gestation. Only very early in utero events could affect IPL lamination in central retina, but events occurring after Fwk 20 in peripheral retina would overlap OPL laminar development in outer retina."
  • A complex choreography of cell movements shapes the vertebrate eye[3] "Optic cup morphogenesis (OCM) generates the basic structure of the vertebrate eye. Although it is commonly depicted as a series of epithelial sheet folding events, this does not represent an empirically supported model. Here, we combine four-dimensional imaging with custom cell tracking software and photoactivatable fluorophore labeling to determine the cellular dynamics underlying OCM in zebrafish."
  • Roles of homeobox genes in retinal ganglion cell differentiation and axonal guidance[4] "In this review, we have described four major families of homeobox genes which play important roles in RGC differentiation as well as axonal pathfinding. The mechanism underlying how these HD TFs affect axonal pathfinding is not entirely known. One possibility is that the downstream targets directly regulated by these HD TF are responsible for axonal guidance. Examples of this are the repression of EphB1 by Isl2, and Vax1/Vax2 regulation of EphB2/EphB3 expression. The roles of Dlx homeobox genes in RGC axonal guidance have not yet been reported. However, in the mouse telencephalon, Dlx1 and Dlx2 promote the tangential migration of GABAergic interneurons by repressing axonal growth (Cobos et al. 2007) and inhibiting Neuropilin-2 expression (Le et al. 2007). It is possible that the genetic program defining RGC identity also encodes a unique "sensory" network for their axons, determining how and where RGC axons respond to guidance cues en route to CNS targets."
More recent papers  
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  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Retina Embryology

Branka Djordjevic, Tatjana Cvetkovic, Tatjana Jevtovic Stoimenov, Milena Despotovic, Slavoljub Zivanovic, Jelena Basic, Andrej Veljkovic, Aleksandra Velickov, Gordana Kocic, Dusica Pavlovic, Dusan Sokolovic Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes. Eur. J. Pharmacol.: 2018; PubMed 29890158

Emma M Coppen, Jeroen van der Grond, Ellen P Hart, Egbert A J F Lakke, Raymund A C Roos The visual cortex and visual cognition in Huntington's disease: an overview of current literature. Behav. Brain Res.: 2018; PubMed 29792890

Hideto Koso, Ryuichi Nishinakamura, Sumiko Watanabe Sall1 Regulates Microglial Morphology Cell Autonomously in the Developing Retina. Adv. Exp. Med. Biol.: 2018, 1074;209-215 PubMed 29721946

Maryo Cenk Kohen, Sinan Tatlipinar, Alev Cumbul, Ünal Uslu The effects of bevacizumab treatment in a rat model of retinal ischemia and perfusion injury. Mol. Vis.: 2018, 24;239-250 PubMed 29681725

Hong Duan, Luis F de Navas, Fuqu Hu, Kailiang Sun, Yannis E Mavromatakis, Kayla Viets, Cyrus Zhou, Joshua Kavaler, Robert J Johnston, Andrew Tomlinson, Eric C Lai ##Title## Development: 2018; PubMed 29540498

Timeline

Human Eye Development
Carnegie Stage Event
10 optic primordia appear.
11 Right and left optic primordia meet at the optic chiasma forming a U-shaped rim.
12 optic neural crest reaches its maximum extent and the optic vesicle becomes covered by a complete sheath,
13 By the end of the fourth week the optic vesicle lies close to the surface ectoderm. Optic evagination differentiation allows identification of optic part of retina, future pigmented layer of retina, and optic stalk. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode.
14 (about 32 days) Lens placode is indented by the lens pit, cup-shaped and still communicates with the surface by a narrowing pore.
15 (about 33 days) Lens pit is closed. The lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface.
16 (37 days) Growth of the lens body results in a D-shaped lens cavity. Perilental blood vessels (tunica vasculosa lentis) are visible. Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it.
17 - 19 Retinal pigment is visible and the retinal fissure is largely closed. Eyelids grooves deepen, eyelid folds develop, first below, and then above, the eye.
18 Mesenchyme invades the region between the lens epithelium and the surface ectoderm.
19 - 22 Eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19.
20 Lens cavity is lost and a lens suture begins to form. The inner canthus is established.
23 retina comprises the pigmented layer, external limiting membrane, proliferative zone, external neuroblastic layer, transient fiber layer, internal neuroblastic layer, nerve fiber layer, and internal limiting membrane. Eyelids closure is complete (Note - shown as still open in the Kyoto embryo).
Data from a study of human embryonic carnegie stages[5] and other sources.
Week: 1 2 3 4 5 6 7 8
Carnegie stage: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Adult Retina

Historic retina drawing.jpg

Eye and retina cartoon.jpg

Vertebrates have ten identifiable layers formed from neurons, their processes (nerve fibers), membranes, photoreceptors and pigmented cells. Light must pass through nearly all these layers to the photoreceptors.

  1. Inner limiting membrane - Müller cell footplates.
  2. Nerve fiber layer - retinal ganglion axons eventually the optic nerve.
  3. Ganglion cell layer - neuronal cell bodies of retinal ganglion cells, their axons form the nerve fiber layer and eventually the optic nerve.
  4. Inner plexiform layer - another layer of neuronal processes.
  5. Inner nuclear layer - neuronal cell bodies
  6. Outer plexiform layer - another layer of neuronal processes.
  7. Outer nuclear layer - neuronal cell bodies
  8. External limiting membrane - layer separating inner segment portions of photoreceptors from their cell nuclei.
  9. Photoreceptor layer - rods and cones that convert light into signals.
  10. Retinal pigment epithelium.


Week 5

Stage 13


Stage 13 image 060.jpgStage 13 image 061.jpg

Week 8

The images below link to virtual slides of the human developing eye at Carnegie stage 22. Click on the image to open or select specific regions from the regions of interest links.

Stage 22 - Eye and Nose

Stage 22 image 008.jpg

 ‎‎Mobile | Desktop | Original

Stage 22 | Embryo Slides
Stage 22 - Eye

Stage 22 image 008-eye.jpg

 ‎‎Mobile | Desktop | Original

Stage 22 | Embryo Slides

Virtual Slide - Regions of Interest

Links: Stage 22 | Embryo Virtual Slides


Stage 22 image 208.jpg Stage 22 image 206.jpg

Retinal Pigment Epithelium

Retinal pigment epithelium (RPE) cells are generated directly from the optic neuroepithelium. The choroidal melanocytes, the other pigmented cells, are derived from neural crest cells that have migrated towards the eye.

Retinal pigment epithelium cells:

  • cuboidal cells
  • apical side form multiple villi
    • these villi are in direct contact with the outer segments of the photoreceptor cells
  • lateral sides are joined together by tight, adherens and gap junctions
  • basal side contacts the underlying basal membrane (Bruch’s membrane)

Ciliary Body

A proposed model of ciliary body development begins with specification at the optic vesicle stage, when the neural retina and pigmented epithelium are also specified. The molecular signals could involve overlapping BMP and FGF signals. The lens has recently been shown in the chicken model to not be required for specification of the iris and ciliary body.[6]

References

  1. Chen J, Ma L, Wang S, Wang X, Sun Y, Gao L, Li J & Zhou G. (2017). Analysis of expression of transcription factors in early human retina. Int. J. Dev. Neurosci. , 60, 94-102. PMID: 28377129 DOI.
  2. Hendrickson A. (2016). Development of Retinal Layers in Prenatal Human Retina. Am. J. Ophthalmol. , 161, 29-35.e1. PMID: 26410132 DOI.
  3. Kwan KM, Otsuna H, Kidokoro H, Carney KR, Saijoh Y & Chien CB. (2012). A complex choreography of cell movements shapes the vertebrate eye. Development , 139, 359-72. PMID: 22186726 DOI.
  4. Zhang Q & Eisenstat DD. (2012). Roles of homeobox genes in retinal ganglion cell differentiation and axonal guidance. Adv. Exp. Med. Biol. , 723, 685-91. PMID: 22183394 DOI.
  5. Pearson AA. (1980). The development of the eyelids. Part I. External features. J. Anat. , 130, 33-42. PMID: 7364662
  6. Dias da Silva MR, Tiffin N, Mima T, Mikawa T & Hyer J. (2007). FGF-mediated induction of ciliary body tissue in the chick eye. Dev. Biol. , 304, 272-85. PMID: 17275804 DOI.

Online Textbooks

  • Kolb H, Fernandez E, Nelson R, editors. Webvision: The Organization of the Retina and Visual System [Internet]. Salt Lake City (UT): University of Utah Health Sciences Center; 1995-. Retinal Neurogenesis: Early stages in the Development of Neurons and Pathways. Available from: https://www.ncbi.nlm.nih.gov/books/NBK52777/

Reviews

{{#pmid: Andreazzoli M. (2009). Molecular regulation of vertebrate retina cell fate. Birth Defects Res. C Embryo Today , 87, 284-95. PMID: 19750521 DOI.

Cvekl A & Wang WL. (2009). Retinoic acid signaling in mammalian eye development. Exp. Eye Res. , 89, 280-91. PMID: 19427305 DOI.

Galli-Resta L, Leone P, Bottari D, Ensini M, Rigosi E & Novelli E. (2008). The genesis of retinal architecture: an emerging role for mechanical interactions?. Prog Retin Eye Res , 27, 260-83. PMID: 18374618 DOI.

Taylor D. (2007). Developmental abnormalities of the optic nerve and chiasm. Eye (Lond) , 21, 1271-84. PMID: 17914430 DOI.

Finlay BL. (2008). The developing and evolving retina: using time to organize form. Brain Res. , 1192, 5-16. PMID: 17692298 DOI.

Cayouette M, Poggi L & Harris WA. (2006). Lineage in the vertebrate retina. Trends Neurosci. , 29, 563-70. PMID: 16920202 DOI.

Bookshelf retina development

Articles

Yao J, Zhou J, Liu Q, Lu D, Wang L, Qiao X & Jia W. (2010). Atoh8, a bHLH transcription factor, is required for the development of retina and skeletal muscle in zebrafish. PLoS ONE , 5, e10945. PMID: 20532172 DOI.

Boije H, Ring H, López-Gallardo M, Prada C & Hallböök F. (2010). Pax2 is expressed in a subpopulation of Müller cells in the central chick retina. Dev. Dyn. , 239, 1858-66. PMID: 20503381 DOI.

Georgi SA & Reh TA. (2010). Dicer is required for the transition from early to late progenitor state in the developing mouse retina. J. Neurosci. , 30, 4048-61. PMID: 20237275 DOI.

Yue F, Johkura K, Shirasawa S, Yokoyama T, Inoue Y, Tomotsune D & Sasaki K. (2010). Differentiation of primate ES cells into retinal cells induced by ES cell-derived pigmented cells. Biochem. Biophys. Res. Commun. , 394, 877-83. PMID: 20206598 DOI.

Levin N, Dumoulin SO, Winawer J, Dougherty RF & Wandell BA. (2010). Cortical maps and white matter tracts following long period of visual deprivation and retinal image restoration. Neuron , 65, 21-31. PMID: 20152110 DOI.

Ghosh F & Arnér K. (2010). Cell type differentiation dynamics in the developing porcine retina. Dev. Neurosci. , 32, 47-58. PMID: 20150723 DOI.

Keeley PW & Reese BE. (2010). Role of afferents in the differentiation of bipolar cells in the mouse retina. J. Neurosci. , 30, 1677-85. PMID: 20130177 DOI.

Sánchez-Sánchez AV, Camp E, Leal-Tassias A & Mullor JL. (2010). Wnt signaling has different temporal roles during retinal development. Dev. Dyn. , 239, 297-310. PMID: 20014102 DOI.

Hackler L, Wan J, Swaroop A, Qian J & Zack DJ. (2010). MicroRNA profile of the developing mouse retina. Invest. Ophthalmol. Vis. Sci. , 51, 1823-31. PMID: 19933188 DOI.

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Cite this page: Hill, M.A. (2018, June 22) Embryology Vision - Retina Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Vision_-_Retina_Development

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