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PubMed2004

Newborn horizontal cells migrate bi-directionally across the neuroepithelium during retinal development.

Cell migration plays an important role during the development of the retina. In this work we have studied the migration of newborn horizontal cells in avian embryonic retina. Using the pattern of the early expressed transcription factors Lim1 and Prox1 we have shown that horizontal cells migrate bi-directionally from their site of birth, close to the ventricular side, to the adjacent (vitreal) side of the neuroepithelium, where they align just next to the prospective ganglion cell layer before migrating back again to their final laminar position in the external part of the inner nuclear layer. The migration occurs between Hamburger and Hamilton stages 24 and 33, which is equivalent to embryonic day 4.5 and 8. Between stages 26 and 30 the horizontal cells reside close to the ganglion cell layer and intra ocular injections of a cytochalasin D, an actin polymerisation blocker that inhibit migration, at stage 29 interfered with the migration of the horizontal cells to their final destination. Furthermore, using biolistic gene transfer with a green fluorescence protein expression vector of retinal slices we were able to record ventricle-directed migration by time-lapse microscopy. Combining biolistics with immunohistochemistry we showed that transfected cells, which have also been translocated in a ventricular direction were positive for the horizontal cell markers Lim1 and Prox1. The alternative path of migration that is described in this work differs from the generally accepted one for horizontal cells and this knowledge will influence the view of how the molecular determination of horizontal cells is specified.

Animals↗
PubMed1999

Evidence for an antiapoptotic role of dopamine in developing retinal tissue.

Inhibition of protein synthesis leads to apoptosis in the undifferentiated neuroblastic layer of the retina of newborn rats. We have shown previously that an increase in the intracellular concentration of cyclic AMP prevented apoptosis induced in the retinal neuroblastic layer by inhibition of protein synthesis. In this study, we tested the effects of dopamine on retinal apoptosis and related these effects to the intracellular concentration of cyclic AMP. Both dopamine (100 microM) and the D1-like agonists SKF-38393, 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (6-Cl-PB), and (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (100 microM) blocked apoptosis induced in the neuroblastic layer by the protein synthesis inhibitor anisomycin. The antiapoptotic effects of the D1-like agonists were not reversed by the D1-like antagonist SCH-23390 (5-100 microM). Both dopamine and D1-like agonists induced a five- to sevenfold increase in the intracellular concentration of cyclic AMP in the retina of newborn rats. The concentration of cyclic AMP induced by the D1-like agonists in the presence of 100 microM SCH-23390 was still at least two- to threefold as high as control values, showing that the activation of adenylyl cyclase by D1-like agonists was reversed only partially by the specific antagonist. The isoquinolinesulfonamide H-89 (20 microM), an inhibitor of cyclic AMP-dependent protein kinase, partially prevented the antiapoptotic effect of 6-Cl-PB. The data show that an early effect of dopamine in the developing retina is the control of programmed cell death. The antiapoptotic effect of dopamine is mediated, at least in part, through an atypical D1-like receptor coupled to stimulation of adenylyl cyclase, followed by activation of cyclic AMP-dependent protein kinase.

Animals↗
PubMed1992

Transient expression of adheron molecules during chick retinal development.

Neuritogenesis and synapse formation are transient phenomena mediated in part by filopodial attachments (Tsui, Lankford, and Klein, Proc. Natl. Acad. Sci. 82:8256-8260 1985). The attachments can be labeled by antisera against adherons, adhesive microparticles isolated from cell culture media (Tsui, Schubert, and Klein, J. Cell Biol. 106:2095-2108 1988). Here, two monoclonal antibodies raised against adherons have been found to recognize transiently expressed membrane antigens of developing avian retina. Early in development, monoclonal antibody (mAb) AD1 stained antigens that spanned the entire tissue. With time, immunoreactivity became restricted to optic fiber, ganglion cell, and inner plexiform layers. Immunoblots of embryonic day (E) 13 retina showed a broad band at 66-72 kD for particulate fractions and a fine band at 70 kD for soluble fractions. The particulate forms disappeared as retinas matured, but the soluble form did not. mAb AD2 initially labeled retina antigens of optic fiber, ganglion cell, and inner plexiform layers (IPL). Labeling in the plexiform layer showed discrete lamina. Immunoreactivity first appeared at E9, peaked at E15, and then disappeared shortly after hatching. In isolated cells, AD2 labeled small cell surface aggregates. Cytoarchitectural studies, using whole-mount transmission electron microscopy, showed AD2 antigen in cell surface microfilaments, including some that joined filopodia together. The adheron antigens recognized by mAbs AD1 and AD2 thus were (1) topographically restricted; (2) associated with cell surfaces; and (3) developmentally down-regulated. This pattern suggests a role in developmentally transient cell surface phenomena, such as neurite extension or junction biogenesis.

Animals↗
PubMed1995

Postnatal retinal development as measured by the electroretinogram in premature infants.

Light-adapted and dark-adapted electroretinograms were obtained in 27 premature infants who were screened for retinopathy of prematurity shortly after birth. Thirteen showed no retinopathy and 13 had mild to moderate retinopathy, which ranged from stage I, zone III (International Classification) to stage III, zone II. Measurements were made during the first 16 months of life. The configuration of the waveforms under both photopic and scotopic conditions changed during this period showing increased amplitudes of both the a- and the b-waves. A scotopic intensity series was performed and the b-wave amplitudes and implicit times were measured. The b-wave amplitude data were averaged for three adult control subjects, for infants without retinopathy of prematurity measured at 3-4 and at 6-7 months and for infants with retinopathy of prematurity measured at 3-4 and at 6-7 months. The Naka-Rushton function was fitted to the average data. The Rmax increased from 3 to 6 months and from 6 months to adulthood, and the Isat values decreased over this age range. The b-wave implicit times were within normal range in the 6-month data. There was no difference in Rmax or Isat for infants with and without ROP.

Adaptation, Ocular↗
PubMed1978

Further studies on the effect of red and far red light on rat retinal development.

The influence on the development of the outer segments of the rat retina of far red and red light in different sequences was investigated. The far red treatment appeared to be dominating, and for animals treated with far red light first, further treatment of red light could not bring the outer segment growth back to normal. The treatments also initiated different dopamine uptakes in the retinas.

Animals↗
PubMed1989

Distribution of retinol isomerase in vertebrate eyes and its emergence during retinal development.

Ocular tissue homogenates were incubated in darkness with [11,12-3H] all-trans retinol. Formation of radiolabeled 11-cis retinol was used as an index of isomerase activity and was determined by high-performance liquid chromatography. Isomerase was found in the eyes of cattle, human, rat, chicken, turtle, goldfish and frog, representing the mammals, birds, reptiles, bony fishes and amphibians. The enzyme was concentrated in the pigment epithelium (RPE). Variable activity was found in the retina, where the amount of radiolabeled 11-cis retinol formed under standard incubation conditions at protein concentrations of 0.03-1.08 mg/ml was 6.4 +/- 6.0% of that in the RPE-choroid. Using the same methodology, we could not detect isomerase in the retinas of three cephalopods (Octopus, Sepia and Loligo). In rats, isomerase was present at postnatal day 10 but not at postnatal days 0 and 4. Therefore, the expression in the RPE of retinol isomerase, which is essential for the formation of rhodopsin in the developing photoreceptors, is coordinated with the emergence of the rod outer segment in the retina. However, the continued expression of this enzyme in RCS rats does not depend on the presence of photoreceptors, because loss of photoreceptors was not associated with an absence of isomerase activity in RCS rats. Our findings suggest that a reciprocal flow of retinoids between the retina and the site of isomerase action in the RPE is a feature common to the visual cycle in all vertebrates.

Animals↗