PubMed Health⌕ Search

Biomedical subjects

Z Q Yin

Publications and source records attributed to Z Q Yin.

10 recordsLinked to original sources

Altered expression of alternatively spliced isoforms of the mRNA NMDAR1 receptor in the visual cortex of strabismic cats.

PURPOSE: Although much has been written about the role of the NMDA receptor's role in experience dependent visual plasticity, the function of the NMDAR1 receptor subunit in the post-plasticity stage of development is still not well understood. However, in the well studied model of strabismic amblyopia where binocularity is reduced, but where most primary visual cortex neurons can be driven by one or other eye, the density of expression of NMDAR1 receptor protein is significantly reduced, compared to normals. This study aims to identify which of eight isoforms of the spliced heterogeneous variants of the NMDAR1 mRNA receptor gene are associated with this decrease in expression as a means of elucidating possible function. METHODS: A series of digoxygenin-labelled oligonucleotide probes based on the human gene sequence have been used for in situ hybridization (ISH) of sections from the striate cortex of four adult cats. The probes were used to uniquely detect the expression of alternatively spliced mRNA variants in 66,487 cells from sections from the area centralis projection of two normal cats and two cats made esotropic as kittens by tenotomy at two weeks of age. RESULTS: As expected, total NMDAR1 mRNA isoform expression was significantly lower in the striate cortex of strabismic compared to normal cats. The proportion of cortical cells expressing the R1-a, R1-b, and R1-1 isoforms in strabismic animals was decreased while the proportion expressing R1-3 was increased, especially in layers V and VI. No significant difference in expression of the R1-2 and R1-4 isoforms was seen comparing strabismic and normal cats. CONCLUSIONS: These results confirm our previous findings and suggest that transcriptional inhibition of specific isoforms of NMDAR1 mRNA may underlie the change in receptor expression. This preferential reduction in the proportion of neurons bearing particular NMDAR1 isoforms, i.e. isoforms R1-a and b, and R1-1 with partial compensation through the expression of the R1-3 isoform, is more likely related to lowered proportion of binocularly activated neurons in the strabismic cat than to changes in eye dominance or the presence of amblyopia in one eye.

Alternative Splicing↗

Transgenic plants expressing autoantigens fed to mice to induce oral immune tolerance.

Oral administration of protein can induce antigen-specific immune hyporesponsiveness. However, the utility of oral tolerance to autoantigens in the treatment of autoimmune diseases may be limited when candidate autoantigens cannot be produced by conventional systems in quantities sufficient for clinical studies. Plants may be ideally suited for this purpose, as they can synthesize, glycosylate and assemble mammalian proteins to provide huge quantities of relatively low cost soluble proteins. Furthermore, edible transgenic plants could provide a simple and direct method of autoantigen delivery for oral tolerance. Therefore, the aim of this study was to determine whether a transgenic plant expression system was capable of synthesizing the diabetes-associated autoantigen, glutamic acid decarboxylase (GAD) in an immunogenic form and whether the oral administration of an autoantigen expressed by a plant could directly induce protective immune responses in a mouse model of diabetes. We show that a GAD-expressing transgenic plant, given as a dietary supplement, inhibits the development of diabetes in the non-obese diabetic (NOD) mouse.

Agrobacterium tumefaciens↗

Cat-301 immunoreactivity in the lateral geniculate nucleus and visual cortex of the strabismic amblyopic cat.

PURPOSE: It was investigated whether alterations in neuronal structure and function occasioned by strabismic amblyopia also may be reflected in alterations in the expression on Y type neurons of a Cat-301 antibody sensitive antigen in the lateral geniculate nucleus (LGN) and cortex of our cat model of strabismic amblyopia. METHODS/RESULTS: The percentage of positively labelled cells was reduced in LGN laminae that received input from the deviated eye in strabismic amblyopic cats compared with normal cats. In the strabismic cortex, the density of immunopositive neurons was significantly reduced compared with normal the effect being most pronounced in layer IV. CONCLUSIONS: Despite previous physiological recordings indicating a decrease in X-cell associated acuity in strabismic amblyopia, the present findings imply that the changes in the early visual experience occasioned by strabismus also produce specific molecular changes in the Y neuronal class.

Amblyopia↗

Widespread choroidal insufficiency in primary open-angle glaucoma.

PURPOSE: The purpose of this study was to investigate choroidal perfusion in glaucoma, using histological and angiographic techniques. METHODS: We examined the choroidal vasculature in clinicopathological slides from 25 cases of primary open-angle glaucoma, five cases of optic atrophy, and 18 normal eyes. We measured choroidal thickness at fixed distances from the disk margin with light microscopy. Using a quantitative computer image analysis system, we established the depth of all vessels and the best fitting diameter and width-to-length ratio for each vessel in three pairs of eyes. Separate statistical analyses were done on the parapapillary area and the whole choroid. We compared standard fluorescein angiographic measures to peak choroidal filling time in a further 78 glaucoma and 84 normal eyes. RESULTS: Choroids were significantly (approximately 50 microns) thinner in glaucoma than in normal or optic atrophy irrespective of fundal position. Vessel frequency and mean diameter, relative to normal, showed greatest decrease near the choriocapillaris. Peak choroidal filling was the only fluorescein angiographic measure that was significantly delayed in glaucoma irrespective of age. CONCLUSIONS: Reduced choroidal thickness in primary open-angle glaucoma is primarily due to loss of the innermost choroidal vessels. Overall size decreases without significant flattening. These changes are not seen with optic atrophy alone and may be correlated with the delayed choroidal perfusion seen in fluorescein angiography.

Aged↗

Distribution and localization of NMDA receptor subunit 1 in the visual cortex of strabismic and anisometropic amblyopic cats.

ACTIVATION of NMDA (N-methyl-D-aspartate) receptors has recently been proposed as a prerequisite for the induction of experience-dependent modification of visual cortical neurones seen during early postnatal development. A new monoclonal antibody to the NMDA receptor subunit 1 (NMDA-R1) has been used to localize and compare the distribution of the receptors in the primary visual cortex of normal cats and those raised with either amblyopia induced by monocular optical blur or monocular esotropic strabismus. Although all three groups showed densest labelling in layers II-III, a comparison of immunopositive cells at any depth below the cortical surface showed a significantly lower frequency in strabismic and anisometropic cats than in normal cats, but a greater frequency in anisometropic cats that in strabismic animals. There appears to be no direct relationship between the expression of NMDA-R1 receptors and the level of excitability, binocularity or neuronal acuity known to exist in either of these two cat models of amblyopia, thus raising further questions as to the precise nature of the role of NMDA receptors in the processes of visual cortical plasticity.

Amblyopia↗

Lupus nephritis in the absence of renal major histocompatibility complex class I and class II molecules.

MRL/Mp-lpr/lpr (MRL-lpr) mice develop an aggressive autoimmune disorder characterized by arthritis, vasculitis, and glomerulonephritis. Renal injury is associated with increased expression of major histocompatibility complex (MHC) molecules, as well as cytokines, adhesion molecules (intracellular adhesion molecule-1, vascular cell adhesion molecule-1), and autoantibodies. By using either MHC Class I (MRL-lpr B2m-/-) or MHC Class II deficient (MRL-lpr Ab-/-) kidneys in a transplant model, we tested the role of renal expression of these molecules in the development of autoimmune renal injury. Kidneys from MRL-lpr B2m-/- or MRL-lpr Ab-/- mice as well as control wild-type mice transplanted into MRL-lpr wt/- recipients developed nephritis, CD4+ and CD8+ T cell infiltration, and heavy glomerular deposition of immunoglobulin. Spontaneously proliferating autoreactive T cells were found in wild-type MRL-lpr and MRL-lpr B2m-/- but not MRL-lpr Ab-/- mice. These results suggest that the absence of renal expression of either Class I or Class II molecules does not provide marked protection from autoimmune lupus nephritis and supports the possibility that protection from autoimmune disease in MRL-lpr Ab-1- mice is related to the loss of autoreactive MHC Class II-dependent CD4+ T cells.

Animals↗

Development of pattern ERG and pattern VEP spatial resolution in kittens with unilateral esotropia.

PURPOSE: To follow the development of strabismic amblyopia longitudinally by comparing mean amplitudes and the visual spatial resolving ability of retinal and cortical pattern responses at various stages of postnatal development in unilateral iatrogenic convergent strabismic kittens. METHODS: Surgery to produce iatrogenic convergent strabismus was performed on 20 kittens at 3 weeks of age; three kittens were used for controls. The monocular transient pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) were recorded simultaneously on the 23 kittens throughout development. RESULTS: The PVEPs of the strabismic eyes were very reduced at 4 to 5 postnatal weeks (P < 0.01). The reduction increased at 6 to 16 weeks but was even worse at 17 to 30 weeks. The PERG of the squinting eye showed only a slight reduction in the first 4 to 5 weeks of age (P > 0.05), the decrease of responses was significant (P < 0.01) at 6 to 16 weeks and 17 to 30 weeks. At 4 to 8 weeks of age, the PVEP evoked through the unoperated eye in kittens consisted mainly of two positive components of similar amplitude. During development, the slow component decreased in comparison to the fast one, and its peak shifted forward until it merged into the fast (P100) component. CONCLUSIONS: Esotropic amblyopia did affect the PERG and the PVEP in the amblyopic eye, but the effect on the PERG was less severe, had slower onset, and did not continue as long as for the PVEP.

Amblyopia↗