Editing Cornea (section)

==Structure==
The cornea has [[myelinated|unmyelinated]] [[nerve]] endings sensitive to touch, temperature and chemicals; a touch of the cornea causes an involuntary [[reflex action|reflex]] to close the [[eyelid]]. Because transparency is of prime importance, the healthy cornea does not have or need [[blood vessel]]s within it. Instead, oxygen dissolves in [[tears]] and then diffuses throughout the cornea to keep it healthy.<ref name="ACLM">{{cite web |publisher=The Association of Contact Lens Manufacturers |url=http://www.aclm.org.uk/index.php?url=04_FAQs/default.php&Q=3 |title=Why does the cornea need oxygen?}}{{MEDRS|date=September 2012}}</ref> Similarly, nutrients are transported via [[diffusion]] from the tear fluid through the outside surface and the [[aqueous humour]] through the inside surface. Nutrients also come via [[neurotrophins]] supplied by the nerves of the cornea. In [[human]]s, the cornea has a diameter of about 11.5&nbsp;mm and a thickness of 0.5–0.6&nbsp;mm in the center and 0.6–0.8&nbsp;mm at the periphery. Transparency, avascularity, the presence of immature resident immune cells, and [[immune privilege|immunologic privilege]] makes the cornea a very special tissue.

The most abundant soluble protein in mammalian cornea is [[albumin]].<ref name="pmid12882779">{{cite journal |last1=Nees |first1=David W. |last2=Fariss |first2=Robert N. |last3=Piatigorsky |first3=Joram |year=2003 |title=Serum Albumin in Mammalian Cornea: Implications for Clinical Application |journal=[[Investigative Ophthalmology & Visual Science]] |volume=44 |issue=8 |pages=3339–45 |pmid=12882779 |doi=10.1167/iovs.02-1161|doi-access=free }}</ref>

The human cornea borders with the [[sclera]] at the [[corneal limbus]]. In [[lamprey]]s, the cornea is solely an extension of the sclera, and is separate from the skin above it, but in more advanced vertebrates it is always fused with the skin to form a single structure, albeit one composed of multiple layers. In fish, and aquatic vertebrates in general, the cornea plays no role in focusing light, since it has virtually the same [[refractive index]] as water.<ref name=VB>{{cite book |last1=Romer |first1=Alfred Sherwood |last2=Parsons |first2=Thomas S. |year=1977 |title=The Vertebrate Body |publisher=Holt-Saunders International |location=Philadelphia |pages=461–2 |isbn=0-03-910284-X}}</ref>

===Microanatomy===
[[File:Vertical section human cornea-Gray871.png|thumb|Vertical section of human cornea from near the margin. (Waldeyer.) Magnified. 1: [[Corneal epithelium|Epithelium]]. 2: [[Bowman's layer|Anterior elastic lamina]]. 3: [[substantia propria]]. 4: [[Descemet's membrane|Posterior elastic lamina]] (Descemet's membrane). 5: [[corneal endothelium|Endothelium]] of the [[anterior chamber]]. a: Oblique fibers in the anterior layer of the [[substantia propria]]. b: Lamellae, the fibers of which are cut across, producing a dotted appearance. c: Corneal corpuscles appearing [[wikt:fusiform|fusiform]] in section.  d: Lamellae, the fibers of which are cut longitudinally. e: Transition to the [[sclera]], with more distinct fibrillation, and surmounted by a thicker [[epithelium]]. f: Small blood vessels cut across near the margin of the cornea.]]
[[File:SD-OCT Corneal Cross-Section.png|thumb|Corneal cross-section imaged by an [[OCT Biomicroscopy#Spectral Domain OCT (SD-OCT)|SD-OCT]]]]

The human cornea has five layers (possibly six, if the [[Dua's layer]] is included).<ref>{{cite web|url=https://www.sciencedaily.com/releases/2013/06/130611084216.htm|title=Scientists discover new layer of the human cornea|website=sciencedaily.com|access-date=14 April 2018}}</ref> Corneas of other [[primate]]s have five known layers. The corneas of cats, dogs, wolves, and other carnivores only have four.<ref name="Merindano">{{cite journal |first1=María Dolores |last1=Merindano Encina |first2=J. M. |last2=Potau |first3=D. |last3=Ruano |first4=J. |last4=Costa |first5=M. |last5=Canals |year=2002|title=A comparative study of Bowman's layer in some mammals Relationships with other constituent corneal structures |journal=European Journal of Anatomy |volume=6 |issue=3 |pages=133–40 |url=http://www.eurjanat.com/web/paper.php?id=02030133}}</ref> From the anterior to posterior the layers of the human cornea are:

# '''[[Corneal epithelium]]''': an exceedingly thin multicellular [[epithelium|epithelial]] tissue layer (non-keratinized stratified squamous epithelium) of fast-growing and easily regenerated [[biological cell|cells]], kept moist with tears. Irregularity or edema of the corneal epithelium disrupts the smoothness of the air/tear-film interface, the most significant component of the total refractive power of the eye, thereby reducing visual acuity. Corneal epithelium is continuous with the conjunctival epithelium, and is composed of about 6 layers of cells which are shed constantly on the exposed layer and are regenerated by multiplication in the basal layer.
# '''[[Bowman's layer]]''' (also known as the ''anterior limiting membrane''): when discussed in lieu of a subepithelial basement membrane, Bowman's Layer is a tough layer composed of [[collagen]] (mainly type I collagen fibrils), [[laminin]], [[nidogen]], [[perlecan]] and other HSPGs that protects the corneal stroma. When discussed as a separate entity from the subepithelial basement membrane, Bowman's Layer can be described as an acellular, condensed region of the apical stroma, composed primarily of randomly organized yet tightly woven collagen fibrils. These fibrils interact with and attach onto each other. This layer is eight to 14 [[micrometre]]s (μm) thick<ref name="ReferenceA">"eye, human."Encyclopædia Britannica from [[Encyclopædia Britannica 2006 Ultimate Reference Suite DVD]] 2009</ref>  and is absent or very thin in non-primates.<ref name="Merindano"/><ref name="NCBI">{{cite journal |doi=10.1002/jmor.10030 |title=Comparative observations on corneas, with special reference to bowman's layer and descemet's membrane in mammals and amphibians |year=2002 |last1=Hayashi |first1=Shuichiro |last2=Osawa |first2=Tokuji |last3=Tohyama |first3=Koujiro |journal=Journal of Morphology |volume=254 |issue=3 |pages=247–58 |pmid=12386895|s2cid=790199 }}</ref>
# '''[[Corneal stroma]]''' (also ''substantia propria''): a thick, transparent middle layer, consisting of regularly arranged collagen fibers along with sparsely distributed interconnected [[corneal keratocyte|keratocytes]], which are the cells for general repair and maintenance.<ref name="ReferenceA"/> They are parallel and are superimposed like book pages. The corneal stroma consists of approximately 200 layers of mainly type I collagen fibrils. Each layer is 1.5-2.5 μm. Up to 90% of the corneal thickness is composed of stroma.<ref name="ReferenceA"/>  There are 2 theories of how transparency in the cornea comes about:
## The lattice arrangements of the collagen fibrils in the stroma. The light scatter by individual fibrils is cancelled by destructive interference from the scattered light from other individual fibrils.<ref>{{Cite journal |doi=10.1113/jphysiol.1957.sp005758 |pmc=1358888 |doi-access=free|year=1957 |last1=Maurice |first1=D. M. |title=The structure and transparency of the cornea |journal=The Journal of Physiology |volume=136 |issue=2 |pages=263–286.1 |pmid=13429485 }}</ref>
## The spacing of the neighboring collagen fibrils in the stroma must be < 200&nbsp;nm for there to be transparency. (Goldman and Benedek)
# '''[[Descemet's membrane]]''' (also ''posterior limiting membrane''): a thin acellular layer that serves as the modified basement membrane of the corneal endothelium, from which the cells are derived. This layer is composed mainly of collagen type IV fibrils, less rigid than collagen type I fibrils, and is around 5-20 μm thick, depending on the subject's age. Just anterior to Descemet's membrane, a very thin and strong layer, Dua's layer, 15 microns thick and able to withstand 1.5 to 2 bars of pressure.<ref>{{cite journal |last1=Dua |first1=Harminder S. |last2=Faraj |first2=Lana A. |last3=Said |first3=Dalia G. |last4=Gray |first4=Trevor |last5=Lowe |first5=James |year=2013 |title=Human Corneal Anatomy Redefined |journal=Ophthalmology |volume=120 |issue=9 |pages=1778–85 |pmid=23714320 |doi=10.1016/j.ophtha.2013.01.018}}</ref>
# [[File:Human eye with limbal ring, anterior view.jpg|thumb|In a healthy eye, the cornea presents as a clear, domed, glossy covering over the [[Iris (anatomy)|iris]] and [[pupil]].]]'''[[Corneal endothelium]]''': a simple [[squamous]] or low [[cuboid]]al monolayer, approx 5 μm thick, of mitochondria-rich cells. These cells are responsible for regulating fluid and solute transport between the aqueous and corneal stromal compartments.<ref name=Cecil>{{cite book |first1=Myron |last1=Yanoff |first2=Douglas |last2=Cameron |chapter=Diseases of the Visual System |chapter-url=https://books.google.com/books?id=Qd-vvNh0ee0C&pg=PA2426 |pages=2426–42 |year=2012 |editor1-first=Lee |editor1-last=Goldman |editor2-first=Andrew I. |editor2-last=Schafer |title=Goldman's Cecil Medicine |edition=24th |publisher=Elsevier Health Sciences |isbn=978-1-4377-1604-7}}</ref> (The term ''endothelium'' is a [[misnomer]] here.  The corneal endothelium is bathed by aqueous humor, not by [[blood]] or [[lymph]], and has a very different origin, function, and appearance from [[endothelium|vascular endothelia]].)  Unlike the corneal epithelium, the cells of the endothelium do not regenerate.  Instead, they stretch to compensate for dead cells which reduces the overall cell density of the endothelium, which affects fluid regulation.  If the endothelium can no longer maintain a proper fluid balance, stromal swelling due to excess fluids and subsequent loss of transparency will occur and this may cause corneal edema and interference with the transparency of the cornea and thus impairing the image formed.<ref name=Cecil /> Iris pigment cells deposited on the corneal endothelium can sometimes be washed into a distinct vertical pattern by the aqueous currents - this is known as [[Krukenberg's Spindle]].

===Nerve supply===
The cornea is one of the most sensitive tissues of the body, as it is densely innervated with sensory nerve fibres via the [[Ophthalmic nerve|ophthalmic division]] of the [[trigeminal nerve]] by way of 70–80 [[long ciliary nerves]]. Research suggests the density of pain receptors in the cornea is 300–600 times greater than skin and 20–40 times greater than [[dental pulp]],<ref>{{cite book|last=Belmonte|first=Carlos|title=Neurobiology of Nociceptors|year=1996|publisher=Oxford University Press|isbn=9780198523345|page=146|author2=Gallar Juana|chapter=6: Corneal Nociceptors|doi=10.1093/acprof:oso/9780198523345.001.0001}}</ref> making any injury to the structure excruciatingly painful.<ref>{{cite web|last=Karmel|first=Miriam|title=Addressing the Pain of Corneal Neuropathy|url=https://www.aao.org/eyenet/article/addressing-pain-of-corneal-neuropathy|work=EyeNet|publisher=American Academy of Ophthalmology|access-date=30 December 2017|date=July 2010}}</ref>

The ciliary nerves run under the endothelium and exit the eye through holes in the sclera apart from the optic nerve (which transmits only optic signals).<ref name="ReferenceA"/> The nerves enter the cornea via three levels; ''scleral, episcleral and conjunctival''. Most of the bundles give rise by subdivision to a network in the stroma, from which fibres supply the different regions. The three networks are, ''midstromal, subepithelial/sub-basal, and epithelial.'' The receptive fields of each nerve ending are very large, and may overlap.

Corneal nerves of the subepithelial layer terminate near the superficial epithelial layer of the cornea in a [[logarithmic spiral]] pattern.<ref name="Yu">{{cite journal |doi=10.1167/iovs.06-1192 |title=Transgenic Corneal Neurofluorescence in Mice: A New Model for in Vivo Investigation of Nerve Structure and Regeneration |year=2007 |last1=Yu |first1=C. Q. |last2=Rosenblatt |first2=M. I. |journal=Investigative Ophthalmology & Visual Science |volume=48 |issue=4 |pmid=17389482 |pages=1535–42|doi-access=free }}</ref> The density of epithelial nerves decreases with age, especially after the seventh decade.<ref>{{cite journal |doi=10.1016/j.exer.2010.07.007 |title=Mapping the entire human corneal nerve architecture |year=2010 |last1=He |first1=Jiucheng |last2=Bazan |first2=Nicolas G. |last3=Bazan |first3=Haydee E.P. |journal=Experimental Eye Research |volume=91 |issue=4 |pages=513–23 |pmid=20650270 |pmc=2939211}}</ref>