Integumentary System - Eyelid Development

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Introduction

The eyelids represent integumentary specialisations that cover and protect the eye cornea.

Note that some species, such as rodents, are born with closed eyelids.

The palpebral commissure (canthus) is located at the corner of the eye where the upper and lower eyelids meet.

Human embryo head showing eyelid development (Stage 22, Week 8)
Embryo head cross-section.
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Some Recent Findings

  • Review - Embryologic and Fetal Development of the Human Eyelid[1] "To review the recent data about eyelid morphogenesis, and outline a timeline for eyelid development from the very early stages during embryonic life till final maturation of the eyelid late in fetal life. METHODS: The authors extensively review major studies detailing human embryologic and fetal eyelid morphogenesis. These studies span almost a century and include some more recent cadaver studies. Numerous studies in the murine model have helped to better understand the molecular signals that govern eyelid embryogenesis. The authors summarize the current findings in molecular biology, and highlight the most significant studies in mice regarding the multiple and interacting signaling pathways involved in regulating normal eyelid morphogenesis. RESULTS: Eyelid morphogenesis involves a succession of subtle yet strictly regulated morphogenetic episodes of tissue folding, proliferation, contraction, and even migration, which may occur simultaneously or in succession."
  • Molecular biology and genetics of embryonic eyelid development[2] "The embryology of the eyelid is a complex process that includes interactions between the surface ectoderm and mesenchymal tissues. In the mouse and human, the eyelids form and fuse before birth; they open prenatally in the human and postnatally in the mouse. In the mouse, cell migration is stimulated by different growth factors such as FGF10, TGF-α, Activin B, and HB-EGF. These growth factors modulate downstream BMP4 signaling, the ERK cascade, and JNK/c-JUN. Several mechanisms, such as the Wnt/β-catenin signaling pathway, may inhibit and regulate eyelid fusion."
More recent papers  
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More? References | Discussion Page | Journal Searches | 2019 References

Search term: Eyelid Embryology | Eyelid Development | meibomian gland |Cryptophthalmia

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.

  • Glucocorticoid receptor antagonizes EGFR function to regulate eyelid development[3] "Eyelid formation constitutes a useful model to study epithelial development, as it requires coordinated regulation of keratinocyte proliferation, apoptosis and migration. ...Our data demonstrate that glucocorticoid receptor (GR) deficiency results in delayed and impaired eyelid closure, as illustrated by increased keratinocyte proliferation and apoptosis along with impaired differentiation in GR(-/-) eyelid epithelial cells."
  • HB-EGF promotes epithelial cell migration in eyelid development[4] "Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors that binds to and activates the EGF receptor (EGFR) and ERBB4. ...These results indicate that soluble HB-EGF secreted from the tip of the leading edge activates the EGFR and ERK pathway, and that synergy with TGFalpha is required for leading edge extension in epithelial sheet migration during eyelid closure."
  • Eyelid fusion and epithelial differentiation at the ocular surface during mouse embryonic development[5] "Eyelid fusion is a critical period for differentiation of the ocular surface ectoderm into the epithelia of the conjunctiva, cornea, and eyelid skin. The conjunctival epithelium differentiates before the corneal epithelium, which in turn differentiates before the eyelid epidermis."

Human Eyelid Timeline

Human Embryonic Eyelid Timeline
Carnegie Stage Event
10 optic primordia appear
13 By the end of the fourth week the optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode.
14 (about 32 days) the lens placode is indented by the lens pit.
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.
16 (37 days) Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it.
17 - 19 grooves deepen, eyelid folds develop, first below, and then above, the eye.
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 the inner canthus is established.
23 closure of the eyelids is complete (Note - shown as still open in some Kyoto embryo).
Data - from Kyoto embryos with Carnegie staging.[6]   Links: eyelid


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: Embryo Virtual Slides


Adult Anatomy

Gray0892.jpg


The palpebral commissure (canthus) is located at the corner of the eye where the upper and lower eyelids meet.

Molecular

See recent article on molecular biology and genetics of embryonic eyelid development.[2]

  • cell migration - FGF10, TGF-α, Activin B, and HB-EGF modulate downstream BMP4 signaling, the ERK cascade, and JNK/c-JUN.
  • Wnt/β-catenin signaling pathway - may inhibit and regulate eyelid fusion.


Abnormalities

 ICD-11 LA14.0 Structural developmental anomalies of eyelids

LA14.00 Palpebral cleft or coloboma

LA14.01 Cryptophthalmia - isolated cryptophtalmia is a congenital abnormality in which the eyelids are absent and skin covers the ocular bulb, which is often microphthalmic.

LA14.02 Congenital entropion - the eyelid (usually the lower lid) folds inward. It is very uncomfortable, as the eyelashes constantly rub against the cornea and irritate it. Entropion is usually caused by genetic factors and very rarely it may be congenital when an extra fold of skin grows with the lower eyelid (epiblepharon).

LA14.03 Congenital ectropion - the lower eyelid turns outwards. It is one of the notable aspects of newborns exhibiting congenital Harlequin-type ichthyosis, but ectropion can occur due to any weakening of tissue of the lower eyelid.

LA14.04 Congenital ptosis - Congenital ptosis is characterised by superior eyelid drop present at birth.

LA14.05 Congenital eyelid retraction

LA14.06 Epibulbar choristoma

LA14.07 Ankyloblepharon filiforme adnatum - Isolated ankyloblepharon filiforme adnatum is characterised by the presence of single or multiple thin bands of connective tissue between the upper and lower eyelids, preventing full opening of the eye.


References

  1. Tawfik HA, Abdulhafez MH, Fouad YA & Dutton JJ. (2016). Embryologic and Fetal Development of the Human Eyelid. Ophthalmic Plast Reconstr Surg , 32, 407-414. PMID: 27124372 DOI.
  2. 2.0 2.1 Rubinstein TJ, Weber AC & Traboulsi EI. (2016). Molecular biology and genetics of embryonic eyelid development. Ophthalmic Genet. , 37, 252-9. PMID: 26863902 DOI.
  3. Sanchis A, Bayo P, Sevilla LM & Pérez P. (2010). Glucocorticoid receptor antagonizes EGFR function to regulate eyelid development. Int. J. Dev. Biol. , 54, 1473-80. PMID: 21136383 DOI.
  4. Mine N, Iwamoto R & Mekada E. (2005). HB-EGF promotes epithelial cell migration in eyelid development. Development , 132, 4317-26. PMID: 16141218 DOI.
  5. Zhang H, Hara M, Seki K, Fukuda K & Nishida T. (2005). Eyelid fusion and epithelial differentiation at the ocular surface during mouse embryonic development. Jpn. J. Ophthalmol. , 49, 195-204. PMID: 15944823 DOI.
  6. Pearson AA. (1980). The development of the eyelids. Part I. External features. J. Anat. , 130, 33-42. PMID: 7364662


Reviews

Zieske JD. (2004). Corneal development associated with eyelid opening. Int. J. Dev. Biol. , 48, 903-11. PMID: 15558481 DOI.

Hamming N. (1983). Anatomy and embryology of the eyelids: a review with special reference to the development of divided nevi. Pediatr Dermatol , 1, 51-8. PMID: 6387662

Articles

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.

Du X, Tabeta K, Hoebe K, Liu H, Mann N, Mudd S, Crozat K, Sovath S, Gong X & Beutler B. (2004). Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice. Genetics , 166, 331-40. PMID: 15020428

Findlater GS, McDougall RD & Kaufman MH. (1993). Eyelid development, fusion and subsequent reopening in the mouse. J. Anat. , 183 ( Pt 1), 121-9. PMID: 8270467

Harris MJ & McLeod MJ. (1982). Eyelid growth and fusion in fetal mice. A scanning electron microscope study. Anat. Embryol. , 164, 207-20. PMID: 7125235

Search PubMed

Search Pubmed: Eyelid Development

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Gray H. Anatomy of the human body. (1918) Philadelphia: Lea & Febiger.

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Cite this page: Hill, M.A. (2019, August 23) Embryology Integumentary System - Eyelid Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Integumentary_System_-_Eyelid_Development

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