Biomedical subjects

F J Lovicu

Publications and source records attributed to F J Lovicu.

27 records · Page 2Linked to original sources

PubMed1997

Expression of FGF-1 and FGF-2 mRNA during lens morphogenesis, differentiation and growth.

PURPOSE: There is now considerable evidence that FGF is involved in lens differentiation and growth throughout life. The aim of this study was to determine potential sites of FGF production in and near the lens during morphogenesis, differentiation and growth. METHODS: The distribution of FGF-1 and FGF-2 mRNAs was analysed in embryonic, weanling and adult rat eyes by in situ hybridization. RESULTS: During lens morphogenesis, there was distinct expression of FGF-1, but not FGF-2, in the lens placode and retinal disc cells. Subsequently, both forms of FGF showed similar expression patterns. During lens differentiation, distinct expression of FGFs was associated with elongating primary fiber cells. From embryonic day 20 onwards, lenses showed strongest expression of FGF mRNAs in the transitional zone, where epithelial cells differentiate into fibers, with weaker expression in the anterior epithelium. Messenger RNAs for both FGFs were also localised in ocular tissues near the lens and bordering the ocular media, particularly the cornea, ciliary body, iris and neural retina. CONCLUSIONS: These findings are consistent with the known distribution of FGF protein in the eye and implicate various ocular tissues as potential sources of FGF that may influence lens cells. Furthermore, the fact that lens cells have the potential for synthesizing FGF, together with evidence from previous studies that lens cells express FGF receptors and respond to lens-derived FGF, raises the possibility that some aspects of lens cell behaviour in situ may be influenced by autocrine mechanism(s) of FGF stimulation.

Animals↗

PubMed1997

Differential expression of fibroblast growth factor receptors during rat lens morphogenesis and growth.

PURPOSE: Fibroblast growth factors (FGF) play important roles in the developmental biology of the lens. Recently, it was shown that the expression of one of the FGF receptors, FGFR1 (flg; fibroblast growth factor receptor 1), was closely associated with the onset of lens fiber differentiation. In this study, the expression patterns of three other members of the FGF receptor family were analyzed and compared. METHODS: The expression patterns of FGFR2 (bek and keratinocyte growth factor receptor [KGFR] variants) and FGFR3 were analyzed by in situ hybridization during embryonic and postnatal lens development. RESULTS: In the ocular primordia, both FGFR2 variants were detected on embryonic day 12 (E12) and FGFR3 was detected on E14. From E16 to E20, distinct spatial expression patterns became evident within the lens; FGFR3 showed an anteroposterior increase in expression, with strongest expression in the outer cortical fibers. In contrast, bek showed uniform expression throughout the lens epithelium (including the central and germinative zones) and the transitional zone, with a subsequent decline in maturing fibers. The KGFR variant of FGFR2 showed strongest expression in the early fibers of the transitional zone; its expression in the epithelium was weaker in the germinative zone of embryonic and neonatal rats. There was an age-related decline in expression of FGFRs after birth-an effect that was more marked for FGFR3 than for the FGFR2 variants. CONCLUSIONS: Combined with those in a previous study, these results indicate that the FGFR1, bek, KGFR, and FGFR3 genes exhibit different, yet overlapping, patterns of expression throughout lens development and differentiation. The distinct spatiotemporal patterns of expression of FGF receptors may play an important role in regulating anteroposterior patterns of lens cell behavior.

Animals↗

PubMed1996

FGF receptor-1 (flg) expression is correlated with fibre differentiation during rat lens morphogenesis and growth.

Our previous studies indicate an important role for fibroblast growth factor (FGF) in lens development. Here we study the expression of the flg variant of FGF receptor 1 (FGFR1) during lens development by immunohistochemistry and in situ hybridisation. FGFR1 was expressed throughout lens development. Prominent FGFR1 immunoreactivity was associated with cell nuclei, particularly in differentiating lens fibres, suggesting internalisation and nuclear translocation of the receptor. FGFR1 immunoreactivity was also associated with basolateral membranes of cells in the equatorial region and at lens sutures. FGFR1 mRNA was only weakly expressed during early lens morphogenesis but expression increased with the onset of lens fibre differentiation. Once the lens acquired its distinct polarity, an anteroposterior gradient in both protein reactivity and mRNA signal was evident. Anteriorly, central epithelial cells showed weak expression for FGFR1, whereas more posteriorly, in the germinative and transitional zones of the lens where cells maximally proliferate and undergo early stages of fibre differentiation, respectively, expression was significantly stronger. The anteroposterior gradient of increased expression of FGFR1 in the lens coincides with the previously documented anteroposterior gradient of FGF stimulation. In lens epithelial explants, FGF stimulation was found to upregulate FGFR1 expression. Such upregulation may be an important mechanism for generating a high level of FGF stimulation and ensuring a fibre differentiation response. In postnatal rat lenses, there was a significant age-related decline in FGFR1 expression; this correlates with the reduced rate of lens fibre differentiation with age. Overall, these studies support the hypothesis that FGF and FGFR1 are important for regulation of lens fibre differentiation throughout lens development.

Animals↗

PubMed1995

Differential effects of aqueous and vitreous on fiber differentiation and extracellular matrix accumulation in lens epithelial explants.

PURPOSE: Results from this and other laboratories strongly suggest that differences in the properties of the ocular media that bathe cells in the anterior and posterior regions of the lens contribute to its normal growth patterns and polarity. The aim of this study was to compare the effects of aqueous and vitreous on the morphology of lens epithelial explants, with particular attention to changes associated with fiber differentiation. METHODS: Light and electron microscopy were used to assess rat lens epithelial explants cultured with bovine aqueous or vitreous. Immunohistochemistry was used to detect fiber-specific crystallins and extracellular matrix components, and synthesis of extracellular matrix was investigated by autoradiography. RESULTS: Vitreous, but not aqueous, induced morphologic changes characteristic of fiber differentiation, which included cell elongation, organelle loss, and the appearance of ball and socket junctions, as well as the accumulation of beta-crystallin. In addition, vitreous stimulated the synthesis and organization of a distinct basement membrane on explants that resembled the lens capsule, both structurally (regular layers of basal laminae) and immunologically (reactive for laminin and heparan sulphate proteoglycan). CONCLUSIONS: Only one of the ocular media, the posteriorly located vitreous, induced lens epithelial explants to undergo morphologic events characteristic of fiber differentiation. This provides further support for the hypothesis that anteroposterior patterns of cellular responses in the lens are caused by differences in the ocular media. The observation that vitreous also stimulated the synthesis and assembly of capsule-like extracellular matrix suggests that vitreous contains factors that may influence lens capsule formation in situ.

Animals↗

PubMed1993

Localization of acidic fibroblast growth factor, basic fibroblast growth factor, and heparan sulphate proteoglycan in rat lens: implications for lens polarity and growth patterns.

PURPOSE: Previous research in this laboratory has shown that fibroblast growth factor stimulates lens epithelial explants to proliferate, migrate, and differentiate into fibers in a progressive dose-dependent manner. The lens has distinct compartments where cells proliferate (germinative zone), migrate, or get displaced (equator) and differentiate into fibers (transitional zone). These compartments occur in an anteroposterior spatial sequence and the authors hypothesized that fibroblast growth factor plays a critical role in determining these spatial patterns of lens growth and lens polarity. To investigate this hypothesis the distribution of fibroblast growth factor in the lens was analyzed. METHODS: Immunohistochemistry was used to localize acidic fibroblast growth factor and basic fibroblast growth factor in the cells and capsule of lenses from neonatal, weanling, and adult rats. Because of its functional relationship with fibroblast growth factor, heparan sulphate proteoglycan was also localized in the lens. RESULTS: In all ages examined, cytoplasmic acidic fibroblast growth factor is present in the germinative and transitional zones of the lens and both acidic fibroblast growth factor and basic fibroblast growth factor are present in the capsule. A major finding is the co-localization of fibroblast growth factor and heparan sulphate proteoglycan reactivity in the lens capsule in the form of laminae. These laminae become more prominent as the capsule thickens and differences in arrangement of laminae between anterior, equatorial, and posterior regions of the capsule also become apparent. CONCLUSIONS: The presence of fibroblast growth factor in lens cells and capsule in neonatal, weanling, and adult rats indicates an important role for fibroblast growth factor in lens cell biology. Moreover, the regional distribution of fibroblast growth factor, particularly in the lens cells, indicates that it may influence determination of lens polarity and growth patterns.

Animals↗

PubMed1992

The age of rats affects the response of lens epithelial explants to fibroblast growth factor. An ultrastructural analysis.

Fibroblast growth factor (FGF) is a potent inducer of fiber differentiation in lens epithelial explants from neonatal rats as assessed by the accumulation of fiber-specific proteins (beta- and gamma-crystallins) and the progression of cells through a sequence of morphologic events characteristic of fiber differentiation in situ. Because new fibers normally are formed in the lens throughout life, the authors questioned whether epithelial cells from rats of all ages are induced to differentiate into fibers by FGF. Earlier studies have shown that, with the increasing age of the donor rat, the lens epithelial explants had a reduced ability to accumulate beta- and gamma-crystallins in response to FGF. To determine if the characteristic morphologic events in fiber differentiation were induced by FGF in explants from rats of different ages, an ultrastructural study was done. Using the time of appearance and level of expression of the following morphologic markers of fiber differentiation: (1) cell elongation, (2) reduction of cytoplasmic organelles, (3) formation of cell processes, and (4) fiber denucleation, the level of fiber differentiation induced by FGF was assessed in explants from 10-, 21-, 100-, and 175-day-old rats. These results showed that, with increasing donor age, epithelial cells showed a gradual decline in responsiveness to FGF. This was manifested by a slower progression through the sequence of fiber-specific structural events as the age of the donor rat increased. At all ages studied, cells in the central region of explants responded more slowly than cells from the peripheral region. The finding that FGF induces events in fiber differentiation, albeit at a slower rate, in explants from mature rats supports the hypothesis that FGF in the eye continues to play a role in inducing lens epithelial cells at the lens equator to differentiate into fibers throughout life.

Aging↗

PubMed1991

The role of fibroblast growth factor in eye lens development.

In this review we have presented evidence that FGF plays an important role in inducing events in lens morphogenesis and growth. Our studies show that FGF stimulates lens epithelial cells in explants to proliferate, migrate, and differentiate into fibers at low, medium, and high concentrations, respectively. This has some important implications for understanding the behavior of lens cells in the eye. The fact that aFGF is detected in the equatorial region of the lens where cells are actively proliferating, possibly migrating, and differentiating into fibers suggests that these events may be under autocrine control in vivo, at least to some extent. Because FGF is also present in the ciliary and iridial region of retina and in the vitreous, paracrine control may also be involved. Cell proliferation, fiber differentiation, and (possibly) cell migration occur in characteristic spatial patterns that are related to distinct compartments of the lens. We suggest that cells in the germinative zone receive only a low level of FGF stimulation arising from the cells themselves and possibly also from the ciliary and iridial regions of the retina but, whatever the source, this is only sufficient to stimulate proliferation. Lens epithelial cells that migrate or are displaced into the transitional zone below the lens equator receive some FGF from these sources but in addition receive a strong stimulus from the high level of FGF in the vitreous; thus, fiber differentiation is induced. Cells at the junction between these two zones may receive an intermediate level of FGF stimulation, sufficient to induce cell migration. In essence, we are proposing that, in the eye, FGF acts as a lens morphogen in the sense that different levels of FGF stimulation elicit different lens cell responses. Hence its characteristic distribution in the eye establishes lens polarity and growth patterns. Since FGF has an inductive effect on lens cells from mature age animals, we also propose that this specific distribution of FGF in the eye is also important for maintenance of a normal lens throughout life. Finally the synergistic effects of insulin/IGF on the FGF-induced responses highlight the importance of considering the distribution of members of the insulin/IGF family of molecules in vivo. Mechanisms that control levels of both the FGF and insulin/IGF families of factors in the eye are probably of crucial importance in the formation and maintenance of a normal lens.

Aging↗

PubMed1989

Structural analysis of lens epithelial explants induced to differentiate into fibres by fibroblast growth factor (FGF).

Recently we identified fibroblast growth factor (FGF), which is present in significant amounts in neural retinas, as a potent inducer of lens fibre differentiation in our epithelial explant cultures. Fibre differentiation was assessed by synthesis of fibre specific, proteins, beta- and gamma-crystallins, and by cell elongation. However, to establish whether FGF induced the dramatic structural changes characteristic of fibre differentiation we carried out an ultrastructural analysis. In this study epithelial explants exposed to either the acidic or basic form of FGF were shown to undergo the structural changes characteristic of fibre differentiation in the intact lens. These include: (i) cell elongation, (ii) a reduction in cytoplasmic organelles, (iii) the formation of specialized cell-cell junctions, including finger-like processes and fingerprints, ball and socket junctions, tongue-like flaps and imprints, and gap junctions, and (iv) nuclear pyknosis. This shows that FGF faithfully reproduces structural events associated with fibre differentiation as well as the molecular events reported previously, thus providing further evidence that FGF in the eye is important for the control of normal lens fibre differentiation.

Animals↗

PubMedDate not supplied

Localization of the extracellular Ca(2+)-sensing receptor in the human placenta.

We have demonstrated using immunohistochemistry and in situ hybridization that the calcium-sensing receptor (CaR) is expressed in both villous and extravillous regions of the human placenta. CaR expression was detected in both first trimester and term placentas. In the villous region of the placenta, the CaR was detected in syncytiotrophoblasts and at lower levels in cytotrophoblasts. Local expression of the CaR in the brush border of syncytiotrophoblasts suggests a role for maternal Ca(2+) concentration in the control of transepithelial transport between the mother and fetus. In the extravillous region of the placenta, the CaR was detected in cells forming trophoblast columns in anchoring villi, in close proximity to maternal blood vessels and in transitional cytotrophoblasts. Given the importance of extravillous cytotrophoblasts in the process of uterine invasion and maintenance of placental immune privilege, the CaR represents a possible target by which the maternal extracellular Ca(2+) concentration could promote or maintain placentation. Thus, the results support hypotheses that the CaR contributes to the local control of transplacental calcium transport and to the regulation of placental development.

Adult↗