The role of growth factors in the embryogenesis and differentiation of the eye

Abstract

The vertebrate eye is composed of a variety of tissues that, embryonically, have their derivation from surface ectoderm, neural ectoderm, neural crest, and mesodermal mesenchyme. During development, these different types of cells are subjected to complex processes of induction and suppressive interactions that bring about their final differentiation and arrangement in the fully formed eye. With the changing concept of ocular development, we present a new perspective on the control of morphogenesis at the cellular and molecular levels by growth factors that include fibroblast growth factors, epidermal growth factor, nerve growth factor, platelet-derived growth factor, transforming growth factors, mesodermal growth factors, transferrin, tumor necrosis factor, neuronotrophic factors, angiogenic factors, and antiangiogenic factors. Growth factors, especially transforming growth factor-beta, have a crucial role in directing the migration and developmental patterns of the cranial neural-crest cells that contribute extensively to the structures of the eye. Some growth factors also exert an effect on the developing ocular tissues by influencing the synthesis and degradation of the extracellular matrix. The mRNAs for the growth factors that are involved in the earliest aspects of the growth and differentiation of the fertilized egg are supplied from maternal sources until embryonic tissues are able to synthesize them. Subsequently, the developing eye tissues are exposed to both endogenous and exogenous growth factors that are derived from nonocular tissues as well as from embryonic fluids and the systemic circulation. The early interaction between the surface head ectoderm and the underlying chordamesoderm confers a lens-forming bias on the ectoderm; later, the optic vesicle elicits the final phase of determination and enhances differentiation by the lens. After the blood-ocular barrier is established, the internal milieu of the eye is controlled by the interactions among the intraocular tissues; only those growth factors that selectively cross the barrier or that are synthesized by the ocular tissues can influence further development and differentiation of the cells. An understanding of the tissue interactions that are regulated by growth factors could clarify the precise mechanism of normal and abnormal ocular development.

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

“…is the generally accepted method. 3T3 cells are either lethally irradiated or growth arrested with mitomycin C and then seeded on tissue culture dishes at 2 3 10 4 cells/cm 2 (117,118).…”

“…In the human embryo, the corneal epithelium is formed by the 6th gestational week, from the surface ectoderm overlying the detaching lens (2). At this stage, it consists of a twolayered epithelium that is separated from the endothelium by an acellular space, the so called primary stroma (3).…”

Protein expression profiling of lens epithelial cells from Prdx6-depleted mice and their vulnerability to UV radiation exposure

“…TGF-␤, a known physiological effecter of various extracellular matrix genes and their products, is present in the aqueous and vitreous humors (90) and has been shown to induce cataracts (28,29,52). Of its three isoforms, TGF-␤1 has been shown to promote tissue fibrosis, formation of stress fiber, epithelial-mesenchymal transition (EMT), myofibroblast formation, fibrosis, and apoptosis by overstimulating genes such as extracellular matrix proteins, ␣-SMA, and ␤ig-h3, which are implicated in several pathogenic conditions (11,79,86,92).…”

Chondroitin Sulphate Proteoglycan is Involved in Lens Vesicle Morphogenesis in Chick Embryos

“…The in¯uence exerted by these edges on differentiation of the lens ®bres has been reported (Tripathi et al, 1991;Wride, 1996), and it is possible that the disappearance or diminishing of CSPG in this region favours contact between both structures and facilitates some in¯uence of the optic cup edges on the lens primordium at this stage of development.…”

“…In addition, there is strong evidence that FGF-2 plays a key role in lens development (McAvoy et al, 1991;Tripathi et al, 1991). It was demonstrated that, in embryonic development, there is a direct functional relationship between FGF-2 and chondroitin sulphate proteoglycan (Ruoslahti and Yamaguchi, 1991;Milev et al, 1998;Colin et al, 1999) or heparan sulphate proteoglycan (Massague, 1991;Yayon et al, 1991;Nugent and Edelman, 1992); these data suggest that the in¯uence of proteoglycans in lens development could be mediated by growth factors.…”