PDGF (alpha)-receptor is unresponsive to PDGF-AA in aortic smooth muscle cells from the NG2 knockout mouse.
A line of null mice has been produced which fails to express the transmembrane chondroitin sulfate proteoglycan NG2. Homozygous NG2 null mice do not exhibit gross phenotypic differences from wild-type mice, suggesting that detailed analyses are required to detect subtle alterations caused by the absence of NG2. Accordingly, dissociated cultures of aortic smooth muscle cells from null mice were compared to parallel cultures from wild-type mice for their ability to proliferate and migrate in response to specific growth factors. Both null and wild-type smooth muscle cells exhibited identical abilities to proliferate and migrate in response to PDGF-BB. In contrast, only the wild-type cells responded to PDGF-AA in both types of assays. NG2 null cells failed to proliferate or migrate in response to PDGF-AA, implying a defect in the signaling cascade normally initiated by activation of the PDGF (alpha)-receptor. In agreement with this idea, activation of the extracellular signal-regulated kinase (ERK) in response to PDGF-AA treatment occured only in wild-type cells. Failure to observe autophosphorylation of the PDGF (alpha)-receptor in PDGF-AA-treated null cells indicates that the absence of NG2 causes a defect in signal transduction at the level of (alpha)-receptor activation. (+info)
Why is the retention of gonadotrophin secretion common in children with panhypopituitarism due to septo-optic dysplasia?
Septo-optic dysplasia (De Morsier syndrome) is a developmental anomaly of mid-line brain structures and includes optic nerve hypoplasia, absence of the septum pellucidum and hypothalamo-pituitary abnormalities. We describe seven patients (four female, three male) who had at least two out of the three features necessary for the diagnosis of septo-optic dysplasia. Four patients had hypopituitarism and yet normal gonadotrophin secretion: one of these also had anti-diuretic hormone insufficiency; three had isolated GH deficiency and yet had premature puberty, with the onset of puberty at least a year earlier than would have been expected for their bone age. In any progressive and evolving anterior pituitary lesion it is extremely unusual to lose corticotrophin-releasing hormone/ACTH and TRH/TSH secretion and yet to retain gonadotrophin secretion. GnRH neurons develop in the nasal mucosa and migrate to the hypothalamus in early fetal life. We hypothesise that the arrival of GnRH neurons in the hypothalamus after the development of a midline hypothalamic defect may explain these phenomena. Progress in spontaneous/premature puberty in children with De Morsier syndrome may have important implications for management. The combination of GH deficiency and premature puberty may allow an apparently normal growth rate but with an inappropriately advanced bone age resulting in impaired final stature. GnRH analogues may be a therapeutic option. In conclusion, some patients with De Morsier syndrome appear to retain the ability to secrete gonadotrophins in the face of loss of other hypothalamic releasing factors. The migration of GnRH neurons after the development of the midline defect may be an explanation. (+info)
Injury-induced gelatinase and thrombin-like activities in regenerating and nonregenerating nervous systems.
It is now widely accepted that injured nerves, like any other injured tissue, need assistance from their extracellular milieu in order to heal. We compared the postinjury activities of thrombin and gelatinases, two types of proteolytic activities known to be critically involved in tissue healing, in nonregenerative (rat optic nerve) and regenerative (fish optic nerve and rat sciatic nerve) neural tissue. Unlike gelatinases, whose induction pattern was comparable in all three nerves, thrombin-like activity differed clearly between regenerating and nonregenerating nervous systems. Postinjury levels of this latter activity seem to dictate whether it will display beneficial or detrimental effects on the capacity of the tissue for repair. The results of this study further highlight the fact that tissue repair and nerve regeneration are closely linked and that substances that are not unique to the nervous system, but participate in wound healing in general, are also crucial for regeneration or its failure in the nervous system. (+info)
Directional and spectral reflectance of the rat retinal nerve fiber layer.
PURPOSE: To measure and describe the reflectance properties of a mammalian retinal nerve fiber layer (RNFL) and to determine the mechanisms responsible for the RNFL reflectance. METHODS: An isolated rat retina suspended across a slit in a black membrane and mounted in a black perfusion chamber provided high quality images of the RNFL. Imaging microreflectometry was used to measure RNFL reflectance at wavelengths from 400 nm to 830 nm and as a function of illumination angle. RESULTS: The directional reflectance of rat RNFL at all wavelengths was consistent with the theory of light scattering by cylinders; each nerve fiber bundle scattered light into a conical sheet coaxial with the bundle. There was no evidence of a noncylindrical component at any wavelength. Measured reflectance spectra were consistent between animals, similar to ones previously measured in macaque, and varied with scattering angle. All spectra could be described by a two-mechanism cylindrical scattering model with three free parameters. CONCLUSIONS: At all wavelengths the reflectance of rat RNFL arises from light scattering by cylindrical structures. The highly directional nature of this reflectance can be an important source of measurement variability in clinical assessment of the RNFL. The reflectance spectra reveal a combination of mechanisms: At wavelengths shorter than approximately 570 nm the reflectance comes from cylinders with diameters much smaller than the wavelength, but at wavelengths longer than approximately 680 nm the reflectance comes from cylinders with effective diameters of 350 nm to 900 nm. (+info)
Test-retest variability of frequency-doubling perimetry and conventional perimetry in glaucoma patients and normal subjects.
PURPOSE: To compare the test-retest variability characteristics of frequency-doubling perimetry, a new perimetric test, with those of conventional perimetry in glaucoma patients and normal control subjects. METHODS: The study sample contained 64 patients and 47 normal subjects aged 66.16+/-11.86 and 64.26+/-7.99 years (mean +/- SD), respectively. All subjects underwent frequency-doubling perimetry (using the threshold mode) and conventional perimetry (using program 30-2 of the Humphrey Field Analyzer; Humphrey Instruments, San Leandro, CA) in one randomly selected eye. Each test was repeated at 1-week intervals for five tests with each technique over 4 weeks. Empirical 5th and 95th percentiles of the distribution of threshold deviations at retest were determined for all combinations of single tests and mean of two tests, stratified by threshold deviation. The influence of visual field eccentricity and overall visual field loss on variability also were examined. RESULTS: Mean test time with frequency-doubling perimetry in patients and normal control subjects was 5.90 and 5.25 minutes, respectively, and with conventional perimetry was 17.20 and 14.01 minutes, respectively. In patients, there was a significant correlation between the results of the two techniques, in the full field and in quadrants, whereas in normal subjects there was no such correlation. In patients, the retest variability of conventional perimetry in locations with 20-dB loss was 120% (single tests) and 127% (mean tests) higher compared with that in locations with 0-dB loss. Comparative figures for frequency-doubling perimetry were 40% and 47%, respectively. Variability also increased more with threshold deviation in normal subjects tested with conventional perimetry. In both patients and normal subjects, variability increased with visual field eccentricity in conventional perimetry, but not in frequency-doubling perimetry. Both techniques showed an increase in variability with overall visual field damage. CONCLUSIONS: Frequency-doubling perimetry has different test-retest variability characteristics than conventional perimetry and may have potential for monitoring glaucomatous field damage. (+info)
CNTF, not other trophic factors, promotes axonal regeneration of axotomized retinal ganglion cells in adult hamsters.
PURPOSE: To investigate the in vivo effects of trophic factors on the axonal regeneration of axotomized retinal ganglion cells in adult hamsters. METHODS: The left optic nerve was transected intracranially or intraorbitally, and a peripheral nerve graft was apposed or sutured to the axotomized optic nerve to enhance regeneration. Trophic factors were applied intravitreally every 5 days. Animals were allowed to survive for 3 or 4 weeks. Regenerating retinal ganglion cells (RGCs) were labeled by applying the dye Fluoro-Gold to the distal end of the peripheral nerve graft 3 days before the animals were killed. RESULTS: Intravitreal application of ciliary neurotrophic factor substantially enhanced the regeneration of damaged axons into a sciatic nerve graft in both experimental conditions (intracranial and intraorbital optic nerve transections) but did not increase the survival of distally axotomized RGCs. Basic fibroblast growth factor and neurotrophins such as nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 failed to enhance axonal regeneration of distally axotomized RGCs. CONCLUSIONS: Neurons of the adult central nervous system can regenerate in response to trophic supply after injury, and ciliary neurotrophic factor is at least one of the trophic factors that can promote axonal regeneration of axotomized RGCs. (+info)
Evaluation of focal defects of the nerve fiber layer using optical coherence tomography.
OBJECTIVE: To analyze glaucomatous eyes with known focal defects of the nerve fiber layer (NFL), relating optical coherence tomography (OCT) findings to clinical examination, NFL and stereoscopic optic nerve head (ONH) photography, and Humphrey 24-2 visual fields. DESIGN: Cross-sectional prevalence study. PARTICIPANTS: The authors followed 19 patients in the study group and 14 patients in the control group. INTERVENTION: Imaging with OCT was performed circumferentially around the ONH with a circle diameter of 3.4 mm using an internal fixation technique. One hundred OCT scan points taken within 2.5 seconds were analyzed. MAIN OUTCOME MEASURES: Measurements of NFL thickness using OCT were performed. RESULTS: In most eyes with focal NFL defects, OCTs showed significant thinning of the NFL in areas closely corresponding to focal defects visible on clinical examination, to red-free photographs, and to defects on the Humphrey visual fields. Optical coherence tomography enabled the detection of focal defects in the NFL with a sensitivity of 65% and a specificity of 81%. CONCLUSION: Analysis of NFL thickness in eyes with focal defects showed good structural and functional correlation with clinical parameters. Optical coherence tomography contributes to the identification of focal defects in the NFL that occur in early stages of glaucoma. (+info)
The optic disc in glaucoma. I: Classification.
Five different descriptive types of glaucomatous optic discs are described, based on the examination of X2 magnification stereophotographs of 252 patients from the files of the Glaucoma Service at Wills Eye Hospital. The method of analysis is described in detail. These types include: overpass cupping, cupping without pallor of the neuroretinal rim, cupping with pallor of the neuroretinal rim, focal notching of the neuroretinal rim, and bean-pot cupping. These morphological types may be caused by variations in factors contributing to the pathogenesis of glaucomatous eyes. Recognition of these differing types may help in determining the factors in each case. (+info)