ISSN 10623604, Russian Journal of Developmental Biology, 2014, Vol. 45, No. 5, pp. 257–266. © Pleiades Publishing, Inc., 2014.
Original Russian Text © V.N. Simirskii, 2014, published in Ontogenez, 2014, Vol. 45, No. 5, pp. 314–325.
The ability of eye tissue for regeneration (wound
healing and/or recovery of the lost part) is widespread
among vertebrates, although the degree of tissue
regeneration varies from species to species. In lower
vertebrates, such as newts, almost all the eye tissue can
regenerate (Mitashov, 2005; Grigoryan et al., 2013). In
higher vertebrates, the tissue regeneration potencies
are more limited and do not always provide the full res
toration (BarbosaSabanero et al., 2012).
The cornea is the transparent anterior avascular
part of the eyeball, which is a direct continuation of
the sclera. The cornea of higher vertebrates consists of
five main layers (Lopashov and Stroeva, 1963; Secker
et al., 2008) (Fig. 1). (1) Corneal epithelium (CE) is an
exfoliated multilayer epithelium that forms the ante
rior surface layer of the cornea. (2) Bowman’s mem
brane is a basal membrane underlying CE. (3) Corneal
stroma is the thickest layer of the cornea (it comprises
85–90% of its thickness). It is formed by a set of par
allel layers of the collagen fibrils; keratocytes, the
fibroblastlike cells secreting the extracellular matrix
are located between them. (4) Descemet’s membrane
is posterior lamina located directly under the stroma.
It is produced by cells of the corneal endothelium and
is its basement membrane. (5) Corneal endothelium is
a singlelayer squamous epithelium. It lines a posterior
surface of the cornea and is directly contacted with the
aqueous humor of the anterior chamber.
Thus, the cornea is formed by three main tissue
types: CE, stroma, and endothelium. CE is actively
renewed due to proliferation of basal layer cells that
differentiate and move to the surface layers, compen
sating the loss of cells from the surface of the cornea
(Collinson et al., 2002). In contrast, stromal kerato
cytes and corneal endothelial cells are in the G
of the cell cycle and divide very rarely (Joyce, 2003;
DelMonte et al., 2011). Corneal injury stimulates the
epithelialmesenchymal transition of CE cells and
activates proliferation of the stromal keratocytes and
the corneal endothelium cells (Kawashima et al.,
2010; DelMonte et al., 2011; Joyce, 2012). The key
point in the disruption of the normal regeneration and
development of fibrosis is the appearance of myofibro
blasts, which actively secrete extracellular matrix (col
lagen, fibronectin, etc.) and prevent the restoration of
the epithelium, forming connective tissue scar at the
tissue injury site (Saika et al., 2008; Wilson, 2012).
Such processes can develop in almost any organ after
its injury (mechanical or due to the impact of unfavor
able factors, such as hypoxia, ultraviolet radiation,
infections, etc.), as well as accompany many chronic
autoimmune diseases (xeroderma, rheumatoid arthri
tis, myelofibrosis, ulcerative colitis). Chronic inflam
mation, changes in vascular permeability, and neovas
cularization (abnormal overgrowth of blood vessels)
also contribute to the disruption of normal tissue
In this review, the features of corneal tissue regen
eration in higher vertebrates and their disruptions
leading to the development of fibrosis are considered.
Particular attention is given to the modern approaches
for the treatment of fibrosis using the methods of cell
and gene therapy.
Regeneration and Fibrosis of Corneal Tissues
V. N. Simirskii
Kol’tsov Institute of Developmental Biology, Russian Academy of Sciences, ul. Vavilova 26, Moscow, 119334 Russia
Received January 16, 2014; in final form, May 6, 2014
—In this review, the features of the regeneration of corneal tissue and its disorders leading to the
development of fibrosis are considered. The data on the presence of stem (clonogenic) cell pool in the corneal
tissues (epithelium, endothelium, stroma) are given; these cells can serve as a source for regeneration of the
tissues at injury or various diseases. The main steps of regeneration of corneal tissues and their disorders that
lead to outstripping proliferation of myofibroblasts and secretion of extracellular matrix in the wound area
and eventually cause the formation of connective tissue scar and corneal opacity are considered. Particular
attention is given to the successes of translational medicine in the treatment of corneal tissue fibrosis. The
methods of cell therapy aimed at the restoration of stem cell pool of corneal tissues are the most promising.
Gene therapy provides more opportunities; one of its main objectives is the suppression of the myofibroblast
proliferation responsible for the development of fibrosis.
: tissue regeneration, fibrosis, epithelialmesenchymal transition, myofibroblasts, stem cell, cell and
gene therapy, cornea