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Biomedical subjects

K Unoki

Publications and source records attributed to K Unoki.

At least 19 recordsLinked to original sources
PubMed1995

[Beneficial effect of a retinoic acid responsive gene product, midkine, on constant light-induced retinal damage in albino mice].

We studied the protective effects of midkine, a growth factor produced by a retinoic acid responsive gene, on constant light-induced retinal damage in albino BALB/C adult mice. Two days before exposure to constant light, midkine was injected into the vitreous of the left eye and a phosphate buffer saline into the right eye (control eyes). After 7 days of constant light, control eyes exhibited shortening of the photoreceptor outer segments and decreased thickness of the outer nuclear layer, whereas in midkine-treated eyes photoreceptor cells were virtually intact. Although midkine-treated eyes also showed photoreceptor damage after longer light exposure of up to 21 days, the damage was significantly less than in control eyes. Measurement of the thickness of the outer nuclear layer showed the protective effect of intravitreous midkine on the constant light-induced retinal damage. These findings suggest that midkine is a potential agent for the prevention of photoreceptor degeneration.

Albinism, Ocular↗
PubMed1995

Functional Rescue of photoreceptors from the damaging effects of constant light by survival-promoting factors in the rat.

PURPOSE: To investigate whether and how survival-promoting agents rescue photoreceptor cell function and morphology from constant light damage, the authors recorded electroretinographic (ERG) responses and examined light micrographs of retinas in those rats given intravitreal injection of midkine (MK) and basic fibroblast growth factor (bFGF) before constant exposure. METHODS: Albino Sprague-Dawley rats were injected with MK, bFGF, or phosphate-buffered saline (PBS) 2 days before the onset of 1 week of constant light. ERG responses were recorded using white flash stimuli with the intensity range of 4 log units, followed by histologic examinations of retinas, including quantitative assessment of the outer nuclear layer thickness as an index of photoreceptor cell loss. RESULTS: ERG responses were barely detectable in uninjected eyes after 1 week of constant light. On the other hand, distinct responses were recordable in eyes injected intravitreally with MK and bFGF, and the degree of ERG rescue in terms of the amplitude of b-wave was approximately 40% to 60% compared with normal eyes. Intravitreally injected PBS showed slight, but noticeable, preservation of ERG responses as well. Histologic examination revealed that MK and bFGF protected photoreceptors from light damage. A good correlation was found between anatomic rescue of photoreceptors as assessed by outer nuclear layer thickness and the functional rescue as defined by the magnitude of ERG responses. CONCLUSIONS: Functional and anatomic rescue of photoreceptors in albino rats from constant light damage is achieved by prior intravitreal injection of MK and bFGF.

Animals↗
PubMed1995

[Binding of amaranthin in human retina].

The binding of amaranthin, specific for Gal beta 1,3 GalNAc and sialic acid Gal beta 1,3 GalNAc sequences, to the human retina was investigated with avidin biotinylated peroxidase. Amaranthin bound to the cone and rod photoreceptors, inner plexiform layer, ganglion cells, and nerve fibers. Since peanut agglutinin, specific for Gal beta 1,3 GalNAc, selectively binds to cones, we conclude that O-glycoside-linked glycoconjugates are present on the surfaces of both cones and rods: Gal beta 1,3 GalNAc and sialic acid Gal beta 1,3 GalNAc are terminal sugars of the glycoconjugates around cones and rods, respectively.

Glycoconjugates↗
PubMed1995

[Distribution of alpha 2,3-sialyltransferase mRNA in rat iris and ciliary body].

The distribution of alpha 2,3-sialyltransferase (alpha 2,3-ST) mRNA in the rat iris and ciliary body was investigated with in situ hybridization histochemistry. Strong expression of alpha 2,3-ST mRNA was detected in the inner epithelial layer of the ciliary body and weak expression in the iris epithelium. Since the synthesis of sialoglycoconjugates is completed by terminal sialylation by the action of sialyltransferase (ST), the ST-expressed portions are considered to produce sialoglycoconjugates. Hence, the source of the sialoglycoconjugates found in the inner epithelial layer of the ciliary body in previous histochemical studies is the same epithelial cell.

Animals↗
PubMed1995

The ultrastructural study of ribosomes in photoreceptor inner segments of the pcd cerebellar mutant mouse.

Ultrastructural changes in the distribution of free ribosomes in photoreceptor inner segments in relation to photoreceptor degeneration in Purkinje cell degeneration (pcd) were studied in mutant mice reared under cyclic light and sacrificed at 30 and 120 postnatal days. On postnatal day 30, some photoreceptors appeared to be normal whereas others had degenerated to varying degrees with numerous spherules in the extracellular space surrounding degenerating inner segments. By postnatal day 120, retinal degeneration had progressed with a marked loss of photoreceptors. The distribution of free ribosomes in the mutant inner segments was random, clustered, or uniform. This was distinct from normal control retinas in which random distribution predominated. Markedly degenerated inner segments contained sparse ribosomes which coalesced in small aggregates. These changes in ribosome distribution seemed to be associated with the extent of photoreceptor degeneration. The significance of these changes in ribosome distribution, in particular clustered distribution, is discussed together with our previous findings.

Animals↗
PubMed1995

Differential expression of mRNA for alpha 2,3-sialyltransferase during development of rat retina.

Glycoconjugates, consisting of O- and N-linked types, are present on the surface of photoreceptor cells and in the interphotoreceptor matrix (IPM). This study was undertaken to facilitate understanding of the metabolic features of O-linked sialoglycoconjugates in comparison with those of N-linked glycoconjugates in the rat retina. We examined the developmental change in distribution of Gal beta 1,3GalNAc alpha 2,3-sialyltransferase mRNA in rat retinas using in situ hybridization histochemistry to detect the synthesis period of O-linked sialoglycans. Positive hybridization signal was observed in the ganglion cells throughout the postnatal days (P) examined, whereas strong signals were detected in the photoreceptor inner segments and the inner nuclear layer exclusively at P16 and P18. At P20 and older, weak or sparse signals were detected in these regions. It is likely that O-linked sialoglycoconjugates, which are detected in the mature IPM, are actively synthesized from P16 to P18 in the rat photoreceptor inner segments, suggesting that the O-linked sialoglycoconjugates in the photoreceptor layer may be stable with litter turnover in the mature retina.

Animals↗
PubMed1994

Binding of amaranthin in photoreceptors of monkey retina.

The binding of amaranthin, specific for the Gal beta 1,3 GalNAc and NeuAc alpha 2,3 Gal beta 1,3 GalNAc sequences, to the photoreceptors of the monkey retina was investigated using the avidin-biotinylated peroxidase method. Amaranthin bound to the surfaces of both cone and rod photoreceptors. This and previous lectin histochemical studies show that O-glycoside-linked glycoconjugates are present on the surfaces of both cones and rods: Gal beta 1,3 GalNAc and NeuAc alpha 2,3 Gal beta 1,3 GalNAc are the terminal sugars of the glycoconjugates around cones and rods, respectively.

Animals↗
PubMed1994

Maackia amurensis lectin binding in developing rat retina.

The developmental changes in the binding of Maackia amurensis lectin, specific for sialic acid alpha 2,3 galactose sequence, to the rat retina was investigated using the avidin-biotinylated peroxidase method. The lectin bound to the surfaces of photoreceptor outer segments from postnatal day 16 (P16), whereas it had bound to the other retinal layers from P14. The intense labelings of the outer segments were interspersed with unstained portions, which may correspond to cone photoreceptors. These results confirm that the sialic acid residues on the terminus of carbohydrate chains increase at P16 and mask the beta-galactose residues around rod outer segments.

Animals↗
PubMed1994

[Light-dependent changes of ribosome distribution in photoreceptor inner segments of the mouse retina].

We studied the distribution pattern of free ribosomes in the photoreceptor inner segments of adult mice with reference to environmental light. Eyeballs were obtained from animals at the light or dark phase of the ordinary cyclic light, and photoreceptor inner segments were examined by electron microscopy. In the light phase, free ribosomes were distributed in a random fashion, although meticulous observations revealed that they appeared to be arranged either in a spiral or linear form, or in isolation. In the dark phase, several free ribosomes were arranged in a clustered fashion. When animals were kept in continuous darkness as long as 27 hours, most of the inner segment free ribosomes showed a clustered pattern similar to that in the dark phase of the cyclic light. We discussed the light-dependent configurational changes of ribosomes with respect to their activity or inactivity in protein synthesis.

Animals↗
PubMed1994

Rescue of photoreceptors from the damaging effects of constant light by midkine, a retinoic acid-responsive gene product.

PURPOSE: To evaluate the protective effects of midkine (MK), the product of a retinoic acid-responsive gene, on constant light-induced retinal degeneration in albino Sprague-Dawley rats. METHODS: Midkine, basic fibroblast growth factor (bFGF), MK plus heparin, or buffer controls were injected intravitreally 2 days before constant light exposure. After 7 days of continuous light exposure, the eyes were perfused with fixative, bisected along the vertical meridian, embedded in paraffin, and sectioned. The degree of retinal light damage was assessed for paraffin-embedded sections by cytologic analysis, by measuring the thickness of the outer nuclear layer (ONL), and by counting the number of macrophages. RESULTS: After 1 week of constant light exposure, uninjected controls and those injected with phosphate-buffered saline (PBS) lost most of the photoreceptor inner and outer segments, and the thickness of the ONL was decreased. Eyes that were injected with MK or bFGF demonstrated a significant rescue in the photoreceptor layer with a two- to threefold increase in the ONL thickness. The number of macrophages in eyes injected with MK was significantly suppressed compared with controls. Those injected with bFGF had a 1.5-fold increase in number compared with controls. CONCLUSIONS: Midkine has shown strong survival-promoting activity in constant light-induced retinal degeneration, and thus has a high degree of neurotrophic activity in vivo.

Animals↗
PubMed1994

Protection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor.

PURPOSE: The protective effects of three survival-promoting agents on ischemia-induced retinal injury in the rat were investigated. The agents included brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and basic fibroblast growth factor (bFGF). METHODS: Retinal ischemia was induced in Lewis albino rats by increasing intraocular pressure to 160 mm Hg for 90 minutes. The agents or buffer controls were injected intravitreally at different times, either before or after the ischemic insult, and the postischemic survival time was either 7 or 14 days. The degree of retinal damage was assessed from plastic-embedded sections by cytologic analysis, measurement of the thickness of several layers, and neuronal counts of the ganglion cell layer. RESULTS: Retinal ischemia thinned and reduced cell numbers in the inner retinal layers, but not in the photoreceptor nuclear layer. Each agent transiently ameliorated the degenerative changes when it was injected 2 days before ischemia. At 7 days postischemia, the inner retinal layers were far less damaged, and more ganglion cells were present than in buffer-injected or uninjected eyes. The protective effect was no longer evident at 14 days postischemia, except in the inner nuclear layer of the BDNF-treated eyes. If a second injection of BDNF was made 5 days after the ischemic insult, then the inner retinal layers were more preserved than buffer controls at 14 days postischemia, but the survival of ganglion cells was not enhanced. A single injection of BDNF at either 1 or 3 days postischemia reduced the degree of inner retinal damage and increased the number of surviving ganglion cells over that in buffer-injected controls. (CNTF and bFGF were not studied with postischemic injections.) CONCLUSIONS: BDNF, CNTF, and bFGF transiently protect the retina from pressure-induced ischemic injury when given 2 days before ischemia, and a second injection of BDNF given postischemically can prolong the protective effect. Moreover, protection afforded by BDNF can be seen even when applied only 1 or 3 days after the ischemic insult, although the protective effect is greater at 1 day than at 3 days postischemia.

Animals↗
PubMed1992

Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light.

Recent demonstrations of survival-promoting activity by neurotrophic agents in diverse neuronal systems have raised the possibility of pharmacological therapy for inherited and degenerative disorders of the central nervous system. We have shown previously that, in the retina, basic fibroblast growth factor delays photoreceptor degeneration in Royal College of Surgeons rats with inherited retinal dystrophy and that the growth factor reduces or prevents the rapid photoreceptor degeneration produced by constant light in the rat. This light-damage model now provides an efficient way to assess quantitatively the survival-promoting activity in vivo of a number of growth factors and other molecules. We report here that photoreceptors can be significantly protected from the damaging effects of light by intravitreal injection of eight different growth factors, cytokines, and neurotrophins that typically act through several distinct receptor families. In addition to basic fibroblast growth factor, those factors providing a high degree of photoreceptor rescue include brain-derived neurotrophic factor, ciliary neurotrophic factor, interleukin 1 beta, and acidic fibroblast growth factor; those with less activity include neurotrophin 3, insulin-like growth factor II, and tumor necrosis factor alpha; those showing little or no protective effect are nerve growth factor, epidermal growth factor, platelet-derived growth factor, insulin, insulin-like growth factor I, heparin, and laminin. Although we used at least one relatively high concentration of each agent (the highest available), it is still possible that other concentrations or factor combinations might be more protective. Injecting heparin along with acidic fibroblast growth factor or basic fibroblast growth factor further enhanced the degree of photoreceptor survival and also suppressed the increased incidence of macrophages produced by either factor, especially basic fibroblast growth factor. These results now provide the impetus for determining the normal function in the retina, mechanism(s) of rescue, and therapeutic potential in human eye diseases for each agent.

Animals↗
PubMed1990

Distribution of glycosyltransferase in bovine eyes.

The activities of sialyl-, fucosyl- and galactosyltransferase were measured in membrane preparations from bovine eyes. Radioactive sugars from CMP-N-neuraminic acid, GDP-fucose and UDP-galactose were incorporated into the endogenous and exogenous acceptors. The enzymatic activities of all three glycosyltransferases were found to be high in the neural retina and retinal pigment epithelium, moderate in the cornea and uvea, and low in the lens and sclera, except for a high galactosyltransferase activity in the cornea.

Animals↗
PubMed1990

The effects of pyrimidine and purine nucleotides on sialyltransferase activity in bovine neurosensory retina.

Effects of nucleotide phosphates on the sialyltransferase activity in the neurosensory retina of the bovine eye were studied. Enzyme activity was assayed using cytidine monophosphate-[14C]-N acetylneuraminic acid as a substrate and desialylated fetuin as an exogenous acceptor. Cytidine-5'-diphosphate and adenosine triphosphate inhibited the enzyme activity. Uridine diphosphate and guanosine diphosphate increased the enzyme activity at low concentrations and decreased the activity at high concentrations. Cyclic adenosine monophosphate and cyclic guanosine monophosphate increased the enzyme activity at concentrations up to 8 mM. It is thus concluded that sialyltransferase activity of the neural retina may be affected by various nucleotides, its alteration depending on either the type of nucleotides or their concentration.

Animals↗
PubMed1989

Pigmentary retinal degeneration in patients with HTLV-I-associated myelopathy.

Ophthalmological evaluations were made of the records of a series of 38 patients with HTLV-I-associated myelopathy, a chronic progressive myelopathy caused by human T-lymphotropic virus type I (HTLV-I). Four patients with no contributory family history showed pigmentary degenerative changes of the retina and choroid. Two of the patients (73-year-old woman, 68-year-old woman) had a progressive visual loss and night blindness with morphologic and functional features of diffuse pigmentary retinal degeneration. The other two patients (59-year-old man, 72-year-old man) complained of recently developed visual loss with sectorial or regional retinochoroidal atrophy. These elderly patients claimed that they had been healthy until a few years before presentation, not only visually but also neurologically. It was concluded, together with an epidemiologic consideration, that the coexistence of pigmentary retinal degeneration and HTLV-I-associated myelopathy is not simply chance but indicates a close association between the two conditions. It is proposed that HTLV-I infection might be a primary causative factor of degenerative changes of the retina and choroid, although the pathogenesis remains to be defined.

Aged↗
PubMed1989

Ocular manifestations in patients infected with human T-lymphotropic virus type I.

Ocular manifestations in patients infected with human T-lymphotropic retrovirus type I (HTLV-I) consisted of a wide range of neoplastic, infectious and noninfectious vascular or inflammatory lesions. These disorders were associated with two distinct HTLV-I-induced systemic diseases, ie, adult T-cell leukemia/lymphoma and HTLV-I-associated myelopathy. Five of the 10 cases of adult T-cell leukemia/lymphoma had inflammatory or opportunistic infectious ocular lesions, including cytomegalovirus retinitis or eyelid tumor as part of generalized lymphomas. Four of the 17 cases of HTLV-I-associated myelopathy showed noninfectious lesions such as isolated, transient cotton-wool spots and granulomatous iridocylitis. Twenty-four (26.9%) of 89 cases with various ocular diseases but no HTLV-I-induced systemic disease had antibodies to HTLV-I in the serum. The aqueous humor antibodies to HTLV-I in the seropositive carriers were negative, except one carrier case who showed isolated cotton-wool spots in one eye and massive vitreous opacities in the other eye.

Adult↗