Vision - Extraocular Muscle Development

From Embryology

Introduction

Human extraocular muscles 01.jpg

These notes introduce the development of the eye muscles. The adult eye has contributions from several different embryonic layers eventually forming neuronal, supportive connective tissue, optical structures, and muscular tissues. Additional pages are being developed to cover specific issues of this anatomical structure.


A study by Gilbert (1957)[1] described the origin and development of the human extrinsic ocular muscles.


Vision Links: vision | lens | retina | placode | extraocular muscle | cornea | eyelid | lacrima gland | vision abnormalities | Student project 1 | Student project 2 | Category:Vision | sensory
Historic Embryology - Vision 
Historic Embryology: 1906 Eye Embryology | 1907 Development Atlas | 1912 Eye Development | 1912 Nasolacrimal Duct | 1917 Extraocular Muscle | 1918 Grays Anatomy | 1921 Eye Development | 1922 Optic Primordia | 1925 Eyeball and optic nerve | 1925 Iris | 1927 Oculomotor | 1928 Human Retina | 1928 Retina | 1928 Hyaloid Canal | Historic Disclaimer
Senses Links: Introduction | placode | Hearing and Balance hearing | balance | vision | smell | taste | touch | Stage 22 | Category:Sensory

Some Recent Findings

  • Eye alignment changes caused by sustained GDNF treatment of an extraocular muscle in infant non-human primates[2] "The ability of sustained treatment of a single extraocular muscle with glial cell line-derived neurotrophic factor (GDNF) to produce a strabismus in infant non-human primates was tested. Six infant non-human primates received a pellet containing GDNF, releasing 2 µg/day for 90 days, on one medial rectus muscle. Eye alignment was assessed up to 6 months. Five of the six animals showed a slow decrease in eye misalignment from the significant exotropia present at birth, ending with approximately 10° of exotropia. Controls became orthotropic. Misalignment averaged 8° three months after treatment ended. After sustained GDNF treatment, few changes were seen in mean myofiber cross-sectional areas compared to age-matched naïve controls. Neuromuscular junction number was unaltered in the medial rectus muscles, but were significantly reduced in the untreated lateral recti. Neuromuscular junctions on slow fibers became multiply innervated after this sustained GDNF treatment. Pitx2-positive cells significantly decreased in treated and contralateral medial rectus muscles. Our study suggests that balanced GDNF signaling plays a role in normal development and maintenance of orthotropia. Sustained GDNF treatment of one medial rectus muscle resulted in a measurable misalignment largely maintained 3 months after treatment ended. Structural changes suggest mechanisms for producing an imbalance in muscle function."
  • Twist3 is required for dedifferentiation during extraocular muscle regeneration in adult zebrafish[3] "Severely damaged adult zebrafish extraocular muscles (EOMs) regenerate through dedifferentiation of residual myocytes involving a muscle-to-mesenchyme transition. Members of the Twist family of basic helix-loop-helix transcription factors (TFs) are key regulators of the epithelial-mesenchymal transition (EMT) and are also involved in craniofacial development in humans and animal models. During zebrafish embryogenesis, twist family members (twist1a, twist1b, twist2, and twist3) function to regulate craniofacial skeletal development. Because of their roles as master regulators of stem cell biology, we hypothesized that twist TFs regulate adult EOM repair and regeneration. In this study, utilizing an adult zebrafish EOM regeneration model, we demonstrate that inhibiting twist3 function using translation-blocking morpholino oligonucleotides (MOs) impairs muscle regeneration by reducing myocyte dedifferentiation and proliferation in the regenerating muscle. This supports our hypothesis that twist TFs are involved in the early steps of dedifferentiation and highlights the importance of twist3 during EOM regeneration."
More recent papers  
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Search term: Extraocular Muscle Development | Extraocular Muscle Embryology | superior rectus development | lateral rectus development | medial rectus development | superior oblique development | inferior oblique development |

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Palisade Endings Are a Constant Feature in the Extraocular Muscles of Frontal-Eyed, But Not Lateral-Eyed, Animals[4] "To test whether palisade endings are a general feature of mammalian extraocular muscles (EOMs). Palisade endings are not a universal feature of mammalian EOMs. So, if they are proprioceptors, not all species require them. Because in frontal-eyed species, the medial rectus muscle has the highest number of palisade endings, they likely play a special role in convergence."
  • Eyelid closure in embryogenesis is required for ocular adnexa development[5] "Mammalian eye development requires temporary fusion of the upper and lower eyelids in embryogenesis. Failure of lid closure in mice leads to an eye open at birth (EOB) phenotype. ...In addition to providing a protective barrier for the ocular surface, eyelid closure in embryogenesis is required for the development of ocular adnexa, including eyelid and extraocular muscles."

Extraocular Muscles

Extraocular muscles are required to move the eye within the orbit. Their embryonic origin requires an interaction between the cranial mesoderm and the migrating neural crest cells.

The following is from a recent paper comparing human to zebrafish muscle development.[6]

About the Muscles Legend
  • Five of the six muscles (inferior rectus, superior rectus, lateral rectus, medial rectus, and superior oblique) originate at a common tendinous ring of fibrous tissue (the Annulus of Zinn).
    • The Annulus of Zinn surrounds the optic nerve, ophthalmic artery, and ophthalmic vein at their entrance through the apex of the orbit.
  • The sixth muscle (inferior oblique) has a separate origin point on the orbital side of the bony maxilla at the anterior inferomedial strut.
  • IR - inferior rectus
  • SR - superior rectus
  • LR - lateral rectus
  • MR - medial rectus
  • SO - superior oblique
  • IO - inferior oblique
Human extraocular muscles 01.jpg

Extraocular muscles (CAT scan back view of the eye)[7]

Extraocular-muscles-scan.jpg

Innervation

Different cranial nerves supple the extraocular muscles.[1]

All the vertebrates:

  • third cranial nerve (CN III) oculomotor nerve supplies - superior rectus, medial rectus, inferior rectus, and inferior oblique
  • fourth cranial nerve (CN IV) trochlear nerve supplies - superior oblique
  • sixth cranial nerve (CN VI) abducens nerve supplies - lateral rectus

In several groups of vertebrates:

  • sixth cranial nerve (CN VI) abducens nerve supplies - retractor bulbi (a seventh eyeball muscle)

Ciliary Muscles

Human Lens (stage 22)

The lens focusses by refracting light as it passes through the biconvex lens, which can be altered in shape (accommodation) by surrounding ciliary muscles. These ciliary muscles are activated (contracted) by parasympathetic innervation from the ciliary ganglion itself innervated by the oculomotor nerve (Cranial Nerve III) (More? Cranial Nerves).

surface ectoderm -> lens placode -> lens pit -> lens vesicle -> lens fibres -> lens capsule and embryonic/fetal nucleus.


Eyelids

Muscles of the eyelids are the Levator palpebræ superiors, Orbicularis oculi and Corrugator. The Orbicularis oculi and Corrugator are both supplied by the facial nerve.
  • The Orbicularis oculi (Orbicularis palpebrarum) arises from the nasal part of the frontal bone, from the frontal process of the maxilla in front of the lacrimal groove, and from the anterior surface and borders of a short fibrous band, the medial palpebral ligament
  • The Corrugator (Corrugator supercilii) is a small, narrow, pyramidal muscle, placed at the medial end of the eyebrow, beneath the Frontalis and Orbicularis oculi.

(modified from Gray's Anatomy)

Gray0379.jpg

Timeline

Embryonic Development

  • Weeks 3 - 4 Eye Fields-Optic Vesicle
  • Weeks 5 - 6 Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
  • Weeks 7 - 8 Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
  • Weeks 9 - 15 Iris, Ciliary Body
  • Weeks 8 - 10 Eyelids
Eye and retina cartoon.jpg

Carnegie Stages - Eye

The following data is from a study of human embryonic carnegie stages[8] and other sources.

  • Stage 10 - optic primordia appear.
  • Stage 11 - right and left optic primordia meet at the optic chiasma forming a U-shaped rim.
  • Stage 12 - optic neural crest reaches its maximum extent and the optic vesicle becomes covered by a complete sheath,
  • Stage 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.
  • Stage 14 - (about 32 days) the lens placode is indented by the lens pit, cup-shaped and still communicates with the surface by a narrowing pore.
  • Stage 15 - (about 33 days) the lens pit is closed. The lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface.
  • Stage 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.
  • Stages 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.
  • Stages 18 - Mesenchyme invades the region between the lens epithelium and the surface ectoderm.
  • Stages 19 - 22 - the 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.
  • Stage 20 - The lens cavity is lost and a lens suture begins to form. The inner canthus is established.
  • Stage 23 - The 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).

Neural Crest

Mouse eye neural crest.jpg

Mouse eye neural crest[9]

Mouse eye TGF-beta model.jpg

Mouse eye TGF-beta model[9]

Links: Image - Mouse eye neural crest | Image - Mouse eye TGF-beta model | Vision Development | Neural Crest Development | Head Development

Additional Images

Historic Images

References

  1. 1.0 1.1 Gilbert PW. The origin and development of the human extrinsic ocular muscles. (1957) Carnegie Instn. Wash. Publ. 611, Contrib. Embryol., Carnegie Inst. Wash. 36: 59-78.
  2. Fleuriet J, Willoughby CL, Kueppers RB, Mustari MJ & McLoon LK. (2020). Eye alignment changes caused by sustained GDNF treatment of an extraocular muscle in infant non-human primates. Sci Rep , 10, 11927. PMID: 32681083 DOI.
  3. Zhao Y, Louie KW, Tingle CF, Sha C, Heisel CJ, Unsworth SP, Kish PE & Kahana A. (2020). Twist3 is required for dedifferentiation during extraocular muscle regeneration in adult zebrafish. PLoS ONE , 15, e0231963. PMID: 32320444 DOI.
  4. Blumer R, Maurer-Gesek B, Gesslbauer B, Blumer M, Pechriggl E, Davis-López de Carrizosa MA, Horn AK, May PJ, Streicher J, de la Cruz RR & Pastor ÁM. (2016). Palisade Endings Are a Constant Feature in the Extraocular Muscles of Frontal-Eyed, But Not Lateral-Eyed, Animals. Invest. Ophthalmol. Vis. Sci. , 57, 320-31. PMID: 26830369 DOI.
  5. Meng Q, Mongan M, Carreira V, Kurita H, Liu CY, Kao WW & Xia Y. (2014). Eyelid closure in embryogenesis is required for ocular adnexa development. Invest. Ophthalmol. Vis. Sci. , 55, 7652-61. PMID: 25377219 DOI.
  6. Kasprick DS, Kish PE, Junttila TL, Ward LA, Bohnsack BL & Kahana A. (2011). Microanatomy of adult zebrafish extraocular muscles. PLoS ONE , 6, e27095. PMID: 22132088 DOI.
  7. Kolb H. Fernandez E. and Nelson R. Webvision: The Organization of the Retina and Visual System. (2012) (Internet) NCBI Bookshelf. PMID 21413389
  8. Pearson AA. (1980). The development of the eyelids. Part I. External features. J. Anat. , 130, 33-42. PMID: 7364662
  9. 9.0 9.1 Ittner LM, Wurdak H, Schwerdtfeger K, Kunz T, Ille F, Leveen P, Hjalt TA, Suter U, Karlsson S, Hafezi F, Born W & Sommer L. (2005). Compound developmental eye disorders following inactivation of TGFbeta signaling in neural-crest stem cells. J. Biol. , 4, 11. PMID: 16403239 DOI.

Online Textbooks

Reviews

Sung CH & Chuang JZ. (2010). The cell biology of vision. J. Cell Biol. , 190, 953-63. PMID: 20855501 DOI.

Heidary G, Engle EC & Hunter DG. (2008). Congenital fibrosis of the extraocular muscles. Semin Ophthalmol , 23, 3-8. PMID: 18214786 DOI.

Shih HP, Gross MK & Kioussi C. (2008). Muscle development: forming the head and trunk muscles. Acta Histochem. , 110, 97-108. PMID: 17945333 DOI. The International Journal of Developmental Biology Vol. 48 Nos. 8/9 (2004) Eye Development

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Cite this page: Hill, M.A. (2020, December 5) Embryology Vision - Extraocular Muscle Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Vision_-_Extraocular_Muscle_Development

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