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Pigment granule migration in isolated cells of the teleost retinal pigment epithelium.

In the teleost eye, the melanin granules of the retinal pigment epithelium (RPE) move in response to changes in light conditions. In the dark, pigment granules aggregate toward the cell base, and in the light, they disperse into long apical projections. Isolated RPE cells from the green sunfish (Lepomis cyanellus) were used to investigate the mechanism and regulation of pigment movement. Changing light conditions did not elicit pigment migration in isolated cells. However, pigment aggregation was induced by 3',5' cyclic-adenosine monophosphate (cAMP), dibutyryl cAMP (dbcAMP), and forskolin (an adenylate cyclase activator). The effectiveness of forskolin suggests that an endogenous adenylate cyclase participates in regulating aggregation. Pigment dispersal was induced by the catecholamines epinephrine, phenylephrine, clonidine, dopamine, and apomorphine. Together the authors' studies suggest: that RPE cells contain the necessary motile machinery to support pigment granule transport in the absence of retina, but not the ability to respond to light; that elevating cAMP induces pigment aggregation; and that catecholamines induce dispersion by binding to receptors on the RPE cell. The authors' observations are consistent with previous suggestions that light regulation of RPE pigment migration is mediated by the retina.

Animals↗

Pigment cells and pigment cell tumors in fish.

The three basic pigment cell types found in poikilothermic vertebrates, melanocytes (melanin-producing cells), erythrophores (red or yellow pigment cells), and iridophores (iridescence-producing cells), are derived from neural crest. Neoplasms of pigment cells in fish are also of three phenotypes, melanomas (melanophoromas), erythrophoromas, and iridophoromas, showing the phenotypes of their corresponding normal pigment cells. These pigment cell tumors are among the most common types in bony fish and seem to be more common in fish than in mammals, including humans. Moreover, there are no mammalian neoplasms corresponding to erythrophoromas and iridophoromas in fish. The complexities in the nature and classification of pigment cell tumors in fish will be discussed on the basis of a survey of our collection of these tumors at the Cancer Institute. The etiology of pigment cell tumors in fish is obscure. In order to know whether activated oncogene is involved in the genesis of erythrophoromas in goldfish, the ras genes from normal and erythrophoroma cells were cloned and their nucleotide sequences were compared. The goldfish ras gene and human ras genes showed striking homology. However, no point mutation at the 12th codon was observed in ras genes isolated from erythrophoromas. Besides pigment cell tumors in fish, abnormal pigmentation or depigmentation in flounders associated with diseased conditions is also described.

Animals↗

In vivo epiluminescence microscopy of pigmented skin lesions. I. Pattern analysis of pigmented skin lesions.

The importance of recognizing early melanoma is generally accepted. Because not all pigmented skin lesions can be diagnosed correctly by their clinical appearance, additional criteria are required for the clinical diagnosis of such lesions. In vivo epiluminescence microscopy provides for a more detailed inspection of the surface of pigmented skin lesions, and, by using the oil immersion technic, which renders the epidermis translucent, opens a new dimension of skin morphology by including the dermoepidermal junction into the macroscopic evaluation of a lesion. In an epiluminescence microscopy study of more than 3000 pigmented skin lesions we have defined morphologic criteria that are not readily apparent to the naked eye but that are detected easily by epiluminescence microscopy and represent relatively reliable markers of benign and malignant pigmented skin lesions. These features include specific patterns, colors, and intensities of pigmentation, as well as the configuration, regularity, and other characteristics of both the margin and the surface of pigmented skin lesions. Pattern analysis of these features permits a distinction between different types of pigmented skin lesions and, in particular, between benign and malignant growth patterns. Epiluminescence microscopy is thus a valuable addition to the diagnostic armamentarium of pigmented skin lesions at a clinical level.

Basal Cell Carcinoma↗

Conditional inhibition of screening-pigment aggregation by lidocaine in crayfish photoreceptors and frog retinal pigment epithelium.

Lidocaine, at concentrations equal to or lower than those that inhibit fast axoplasmic transport, was found to interfere with the dark-adapting migration of the screening pigments along crayfish photoreceptors and within the cells of the frog retinal pigment epithelium (RPE). The effects of the anesthetic on pigment movements were studied in isolated eyes incubated under light or dark conditions in media of different ionic compositions. Treatment of crayfish eyes with 25 mmol l-1 lidocaine in normal Van Harreveld's saline arrested pigment migration to the dark-adapted position or caused migration towards the light-adapted position in the dark. Similar results were obtained with frog eyecups exposed to 5 mmol l-1 lidocaine in Ringer's solution. In each case, the inhibition of dark adaptation was reversible and dependent on the levels of Na+ and Ca2+ in the incubation medium. A dark-adapted position of both pigments was compatible with lidocaine treatment provided that low-Na+, or high-Ca2+ or Co(2+)-containing solutions were used. These results indicate that light-adapted and dark-adapted pigment positions in both types of retinal cells can occur in the absence of local nervous input. Further, the data suggest a direct effect of lidocaine upon the photoreceptors or RPE cells. The inhibition of pigment aggregation is interpreted to be a consequence of an anesthetic-induced increase in the permeability of the plasma membrane, which in turn affects the intracellular ionic balance that controls pigment position.

Adaptation, Ocular↗

Retinal pigment epithelial dysfunction in patients with pigment dispersion syndrome: implications for the theory of pathogenesis.

OBJECTIVE: To test the hypothesis that the retinal pigment epithelial/photoreceptor complex is affected in patients with pigment dispersion syndrome and/or in patients with pigmentary glaucoma. METHODS: Electro-oculograms were recorded from patients with pigment dispersion syndrome, pigmentary glaucoma, ocular hypertension, and primary open-angle glaucoma and from control subjects. Electro-oculograms were recorded during 15 minutes of dark adaptation followed by 15 minutes of light adaptation. For each subject, dark-trough amplitudes, dark-trough latencies, light-peak amplitudes, light-peak latencies, and ratios of the light-peak amplitude to the dark-trough amplitude (Arden ratios) were calculated. RESULTS: A 1-way analysis of variance of the Arden ratios indicated significant differences among the groups of subjects. Results of a post hoc Newman-Keuls test revealed that the mean Arden ratios of patients with pigment dispersion syndrome and patients with pigmentary glaucoma were significantly lower than the mean ratios of the controls, the patients with primary open-angle glaucoma, and those with ocular hypertension. CONCLUSIONS: The results provide support for the hypothesis that the integrity of the retinal pigment epithelial/photoreceptor complex is affected in patients with pigment dispersion syndrome and in those with pigmentary glaucoma. Congenital and/or structural abnormalities of the retinal pigment epithelial/photoreceptor complex should be considered when models of the etiology of pigment dispersion syndrome are proposed.

Adult↗

Murine and bovine blue cone pigment genes: cloning and characterization of two new members of the S family of visual pigments.

Two novel visual pigment genes, mouse blue and bovine blue, have been isolated from mouse and bovine genomic libraries, respectively, using a human blue cone pigment cDNA as probe. Corresponding cDNA clones have also been obtained from mouse retinas. The intron-exon boundaries for the mouse gene were determined by comparing the genomic and cDNA sequences. The visual pigments encoded by the mouse and bovine blue pigment genes are highly homologous to each other (89% amino acid identity) and to human blue and chicken violet cone pigments (greater than 80% identity), but are less homologous to chicken or goldfish blue cone pigments (less than 50% identity). These results indicate that phylogenetically both mouse and bovine blue pigments belong to the S branch of visual pigments, rather than to the M branch.

Amino Acid Sequence↗

Pigmented ameloblastic fibrodentinoma: a novel melanin-pigmented intraosseous odontogenic lesion.

This paper reports about an ameloblastic fibrodentinoma with macroscopically visible pigmentation, resulting in the clinical appearance of a melanotic lesion in a 21-year-old Japanese male. In addition to the characteristic histopathologic features of ameloblastic fibrodentinoma, various-formed and -sized cells, which were considered to be melanophages containing numerous aggregates of melanin pigment in their cytoplasm, were densely distributed throughout the mesenchymal component. In addition, melanin pigment was deposited in dentin. Some of the pigmented cells showed dendritic form and were regarded as melanocytes. Furthermore, pigmented cells were frequently distributed in the epithelial component, and melanin pigment was seen in some epithelial cells. Perusal of the English language literature revealed 30 cases of pigmented odontogenic tumors: 18 were calcifying odontogenic cysts, three were ameloblastic fibro-odontomas, three were adenomatoid odontogenic tumors, two were odontomas, one was an ameloblastic fibroma and one was an odontogenic fibroma. However, all of these reported lesions did not show macroscopically visible pigmentation. The possible histogenesis of melanocytes in the odontogenic lesions is discussed, although no firm conclusion could be drawn.

Adult↗

Actin-dependent, retrograde motility of surface-attached beads and aggregating pigment granules in dissociated teleost retinal pigment epithelial cells.

Teleost retinal pigment epithelial (RPE) cells contain pigment granules within apical projections which undergo actin-dependent, bi-directional motility. Dissociated RPE cells in culture attach to the substrate and extend apical projections in a radial array from the central cell body. Pigment granules within projections can be triggered to aggregate or disperse by the presence or absence of 1 mM cAMP. Aminated, fluorescent latex beads attached to the dorsal surface of apical projections and moved in the retrograde direction, towards the cell body. Bead rates on RPE cells with aggregating or fully aggregated pigment granules were 2.2 +/- 0.5 and 2.6 +/- 0.2 microm/min (mean +/- SEM), respectively, similar to rates of aggregating (retrograde) pigment granule movement (2.0 +/- 0.4 microm/min). Bead rates were slightly slower on cells with fully dispersed or dispersing pigment granules (1.5 +/- 0.1 and 1.5 +/- 0.4 microm/min). Movements of surface-attached beads and aggregating pigment granules were closely correlated in the distal portions of apical projections, but were more independent of each other in proximal regions of the projections. The actin disrupting drug, cytochalasin D (CD), reversibly halted retrograde bead movements, suggesting that motility of surface-attached particles is actin-dependent. In contrast, the microtubule depolymerizing drug, nocodazole, had no effect on retrograde bead motility. The similar characteristics and actin-dependence of retrograde bead movements and aggregating pigment granules suggest a correlation between these two processes.

Actins↗

Molecular properties of rod and cone visual pigments from purified chicken cone pigments to mouse rhodopsin in situ.

We have investigated the molecular properties of rod and cone visual pigments to elucidate the differences in the molecular mechanism(s) of the photoresponses between rod and cone photoreceptor cells. We have found that the cone pigments exhibit a faster pigment regeneration and faster decay of meta-II and meta-III intermediates than the rod pigment, rhodopsin. Mutagenesis experiments have revealed that the amino acid residues at positions 122 and 189 in the opsins are the determinants for these differences. In order to study the relationship between the molecular properties of visual pigments and the physiology of rod photoreceptors, we used mouse rhodopsin as a model pigment because, by gene-targeting, the spectral properties of the pigment can be directly correlated to the physiology of the cells. In the present paper, we summarize the spectroscopic properties of cone pigments and describe our studies with mouse rhodopsin utilizing a high performance charge coupled device (CCD) spectrophotometer.

Animals↗

Dense pigmentation of the posterior lens capsule associated with the pigment dispersion syndrome.

PURPOSE: To report an unusual case of pigment dispersion syndrome associated with unilateral dense pigmentation of the posterior lens capsule. METHODS: Case report. RESULTS: A 59-year-old male with bilateral pigment dispersion syndrome presented with progressive decrease in visual acuity in the left eye over the past 10 to 20 years. Clinical examination revealed the typical findings of pigment dispersion syndrome including the presence of bilateral Krunkenberg spindles, iris transillumination defects, and heavy trabecular meshwork pigmentation. Of note, there was remarkably dense pigmentation of the posterior lens capsule in the eye with decreased visual acuity. CONCLUSION: Pigmentation of the posterior lens capsule may be a rare finding associated with pigment dispersion syndrome. Such a finding suggests that there may be aqueous flow into the retrolental space in some patients with this condition. The optimal treatment of this unusual condition remains undetermined.

Exfoliation Syndrome↗

The time course of photoadaptation and pigmentation studied using a novel method to distinguish pigmentation from erythema.

The dynamics of human pigmentation in response to ultraviolet radiation (UVR) remain poorly characterized. In part, this is attributable to methodological issues relating to the overlap in spectra of hemoglobin and melanin. We describe a new method, based on the recording of reflectance properties following iontophoresis of a potent vasoconstrictor, noradrenaline. This removes the influence of blood, allowing measurement of pigmentation, represented as L* on the L*a*b* scale. Blood flow was separately assessed using laser Doppler flowmetry. We show that there is a clear dose response with the dose of UVR administered, that pigmentation peaks at 1 wk and declines over the following 10 wk, but does not return to baseline within this period. We show clear differences in the degree, but not the temporal pattern of pigmentation between different pigmentary groups. We also report that the relation between facultative pigment and constitutive pigment is incomplete, with a wide scatter of responses for the development of pigmentation irrespective of constitutive levels. For comparison we also document overall photoadaptation and relate changes in pigmentation to the overall changes in photoadaptation.

Adaptation, Physiological↗

Studies on guinea pig skin cell cultures. V. Co-culture of pigmented melanocytes and albino keratinocytes, a model for the study of pigment transfer.

Mixed cultures of melanocytes (M) and keratinocytes (K) are easily obtained from pigmented guinea pig ear skin. They are suitable for the study of pigment transfer from M to K. However, quantitation is difficult because many K are already loaded with pigment prior to cultivation. A technique is presented in which pigment-producing M are co-cultured with K of albino origin. Pigmented guinea pig ear skin is split with trypsin and basal cells including M are harvested. The cell suspension is treated with sodium citrate which prevents the attachment of K (but not of M) to the culture substrate. Ninety per cent pure M cultures are obtained. Five to seven days later, another basal cell suspension is prepared, this time from albino ear skin. This second suspension is seeded on top of the pigment-forming culture of M. The number of contacts between albino K and pigment-forming M increases as a direct function of time. Contrarily, the number of K which become pigmented increases until the fifth day of co-culture and decreases thereafter.

Animals↗

Formalin pigment (acid hematin) and related pigments.

Black to brown amorphous to microcrystalline granules are encountered in histologic sections prepared from tissues fixed in formalin having a low pH. This pigment is produced by acid acting upon hemoglobin and is known as formalin pigment or acid hematin. A similar pigment is also observed in sites of bleeding ulcers in areas of acid production such as the stomach. These pigments exhibit many physical and histochemical properties similiar to pigments produced by some animal parasites as in malaria, schistosoma and pulmonary mites. These parasites disintegrate erythrocytes in an unknown manner, and liberate an acid hematin-like pigment which is phagocytized by the reticuloendothelial system. Since formalin pigment can be considered as an artifact, confusion with other pigments can be avoided by the use of neutral buffered formalin for the fixation of tissues.

Animals↗