Corneal Keratocyte
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Corneal keratocytes (corneal fibroblasts) are specialized
fibroblast A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...
s residing in the stroma. This
cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...
l layer, representing about 85-90% of corneal thickness, is built up from highly regular collagenous lamellae and extracellular matrix components. Keratocytes play the major role in keeping it transparent, healing its wounds, and synthesizing its components. In the unperturbed cornea keratocytes stay dormant, coming into action after any kind of injury or inflammation. Some keratocytes underlying the site of injury, even a light one, undergo
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
immediately after the injury. Any glitch in the precisely orchestrated process of healing may cloud the cornea, while excessive keratocyte apoptosis may be a part of the pathological process in the degenerative corneal disorders such as
keratoconus Keratoconus is an eye disorder in which the cornea, the transparent front part of the eye, gradually thins and bulges outward into a cone shape. This causes distorted vision, including blurry vision, double vision, increased nearsightedness, ...
, and these considerations prompt the ongoing research into the function of these cells.


Origin and functions

Keratocytes are developmentally derived from the cranial population of
neural crest The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, ...
cells, from whence they migrate to settle in the
mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood, or bone. The interactions between mesenchyme and epithelium help to form nearly ever ...
. In some species the migration from neural crest comes in two waves, with the first giving birth to the
corneal endothelium The corneal endothelium is a single layer of endothelial cells on the inner surface of the cornea. It faces the chamber formed between the cornea and the iris. The corneal endothelium are specialized, flattened, mitochondria-rich cells that ...
and the second invading the epithelium-secreted stromal anlage devoid of cells; in other species both populations come from a single wave of migration. Once settled in the stroma, keratocytes start synthesizing collagen molecules of different types (I, V, VI) and
keratan sulfate Keratan sulfate (KS), also called keratosulfate, is any of several sulfated glycosaminoglycans (structural carbohydrates) that have been found especially in the cornea, cartilage, and bone. It is also synthesized in the central nervous system whe ...
. By the moment of eye opening after birth the proliferation of keratocytes is all but finished and most of them are in the quiescent state. By the end of eye development an interconnected keratocyte network is established in the cornea, with
dendrites A dendrite (from Greek δένδρον ''déndron'', "tree") or dendron is a branched cytoplasmic process that extends from a nerve cell that propagates the electrochemical stimulation received from other neural cells to the cell body, or soma ...
of neighbouring cells contacting each other. Quiescent keratocytes synthesize the so-called
crystallin In anatomy, a crystallin is a water-soluble structural protein found in the lens and the cornea of the eye accounting for the transparency of the structure. It has also been identified in other places such as the heart, and in aggressive breast ...
s, known primarily for their role in the
lens A lens is a transmissive optical device that focuses or disperses a light beam by means of refraction. A simple lens consists of a single piece of transparent material, while a compound lens consists of several simple lenses (''elements'') ...
. Corneal crystallins, like the lens ones, are thought to help maintain the transparency and optimal refraction. They are also part of corneal antioxidant defense. Crystallins expressed by human keratocytes are
ALDH1A1 Aldehyde dehydrogenase 1 family, member A1, also known as ALDH1A1 or retinaldehyde dehydrogenase 1 (RALDH1), is an enzyme that is encoded by the ''ALDH1A1'' gene. Function This protein belongs to the aldehyde dehydrogenases family of proteins ...
, ALDH3A1,
ALDH2 Aldehyde dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ''ALDH2'' gene located on chromosome 12. ALDH2 belongs to the aldehyde dehydrogenase family of enzymes. Aldehyde dehydrogenase is the second enzyme of the majo ...
and TKT. Different sets of crystallins are typical to distinct species. Keratan sulfate produced by keratocytes is thought to help maintain optimal corneal hydration; genetic disruption of its synthesis leads to the
macular corneal dystrophy Macular corneal dystrophy, also known as Fehr corneal dystrophy, is a rare pathological condition affecting the stroma of cornea first described by Arthur Groenouw in 1890.Groenouw A. Knötchenförmige Hornhauttrübungen (noduli corneae). Arch Aug ...
.MACULAR DYSTROPHY, CORNEAL, 1; MCDC1
-
OMIM Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM ...
.
According to one study, average keratocyte density in the human stroma is about 20500 cells per mm3, or 9600 in a column of 1 mm2 in section. The highest density is observed in the upper 10% of the stroma. The number of keratocytes declines with age, at a rate approximately 0.45% per year. After an injury to the cornea, some keratocytes undergo apoptosis, prompted by the signaling molecules secreted by the upper layers, such as IL1 alpha and
TNF-alpha Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...
. Other neighbouring keratocytes, when acted upon by the same molecules, become active, proliferate and start synthesizing
matrix metalloproteinase Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs be ...
s that cause tissue remodeling. These activated cells are designated in different sources either as "active keratocytes" or "fibroblasts" or are said to assume a "repair phenotype". After heavier injuries or at the advanced stages of healing process a number of keratocytes transforms into
myofibroblast A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell. Structure Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-s ...
s actively secreting
ECM ECM may refer to the following: Economics and commerce * Engineering change management * Equity capital markets * Error correction model, an econometric model * European Common Market Mathematics * Lenstra's Elliptic curve method for factor ...
components; this transformation is thought to be caused by
TGF-beta Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other ...
. As soon as the
basement membrane The basement membrane, also known as base membrane, is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tis ...
of
corneal epithelium The corneal epithelium (epithelium corneae anterior layer) is made up of epithelial tissue and covers the front of the cornea. It acts as a barrier to protect the cornea, resisting the free flow of fluids from the tears, and prevents bacteria fr ...
is restored,
TGF beta Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the Transforming growth factor beta family, transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HUGO Gene Nomen ...
inflow into the stroma drastically decreases and myofibroblasts disappear, after which the remaining activated keratocytes continue for some time to reshape the extracellular matrix, secreting IL1-alpha in order to maintain their "repair phenotype".
Apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
of keratocytes, either in quiescent or active state, is a process that attracts special attention. In a healthy
cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...
the programmed
cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...
death Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...
is a rare occasion, but immediately after an
injury Injury is physiological damage to the living tissue of any organism, whether in humans, in other animals, or in plants. Injuries can be caused in many ways, including mechanically with penetration by sharp objects such as teeth or with ...
to the uppermost layer keratocytes directly under the injury site commit apoptosis. One
hypothesis A hypothesis (: hypotheses) is a proposed explanation for a phenomenon. A scientific hypothesis must be based on observations and make a testable and reproducible prediction about reality, in a process beginning with an educated guess o ...
explains such rapid reaction by the need to stem the possible
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
from spreading into the cornea, because due to the limitations of ocular immune system the
immune cells White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
take up to several
hour An hour (symbol: h; also abbreviated hr) is a unit of time historically reckoned as of a day and defined contemporarily as exactly 3,600 seconds ( SI). There are 60 minutes in an hour, and 24 hours in a day. The hour was initially establis ...
s to arrive at the site of injury. In a normal course of events, the lack of keratocytes is gradually replenished by the
mitosis Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...
of the adjacent cells. Apoptosis is observed after eye operations, including keratotomy and
laser surgery Laser surgery is a type of surgery that cuts tissue using a laser in contrast to using a scalpel. Soft-tissue laser surgery is used in a variety of applications in humans ( general surgery, neurosurgery, ENT, dentistry, orthodontics, and ...
, and may play a role in the development of post-surgery complications.


Clinical significance

Keratocytes may play a role in different corneal disorders. According to comparative research, their functions drastically diverge from the norm in
keratoconus Keratoconus is an eye disorder in which the cornea, the transparent front part of the eye, gradually thins and bulges outward into a cone shape. This causes distorted vision, including blurry vision, double vision, increased nearsightedness, ...
, the most frequent form of
corneal dystrophy Corneal dystrophy is a group of rare hereditary disorders characterised by bilateral abnormal deposition of substances in the transparent front part of the eye called the cornea. Signs and symptoms Corneal dystrophy may not significantly affect ...
. In keratoconic corneas they have been shown to commit apoptosis far away from any epithelial injury; a hypothesis exists that presents excessive keratocyte apoptosis as a major pathological event in keratoconus. According to one study, patient's keratocytes have decreased levels of one of the alcohol dehydrogenase subforms, they secrete significantly less superoxide dismutase 3, according to another.


See also

*
List of human cell types derived from the germ layers This is a list of Cell (biology), cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm. Cells derived from ectoderm Surface ectoderm Skin * Trichocyte (human), Trichocyte * Keratinocyte Anterior pi ...


References


External links


Nigel Brookes
- researcher {{eye Cells Ophthalmology