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Carotenoid pigments and the selectivity of psittacofulvin-based coloration systems in parrots.

Carotenoid pigments are commonly used as colorants of feathers and bare parts by birds. However, parrots (Aves: Psittaciformes) use a novel class of plumage pigments (called psittacofulvins) that, like carotenoids, are lipid-soluble and red, orange, or yellow in color. To begin to understand how and why parrots use these pigments and not carotenoids in their feathers, we must first describe the distribution of these two types of pigments in the diet, tissues, and fluids of these birds. Here, we studied the carotenoid content of blood in five species of parrots with red in their plumage to see if they show the physiological ability to accumulate carotenoids in the body. Although Scarlet (Ara macao) and Greenwing Macaws (Ara chloroptera) and Eclectus (Eclectus roratus), African Gray (Psittacus erithacus) and Blue-fronted Amazon (Amazona aestiva) Parrots all use psittacofulvins to color their feathers red, we found that they also circulated high concentrations of both dietary (lutein, zeaxanthin, beta-cryptoxanthin) and metabolically derived (anhydrolutein, dehydrolutein) carotenoids through blood at the time of feather growth, at levels comparable to those found in many other carotenoid-colored birds. These results suggest that parrots have the potential to use carotenoids for plumage pigmentation, but preferentially avoid depositing them in feathers, which is likely under the control of the maturing feather follicle. As there is no evidence of psittacofulvins in parrot blood at the tune of feather growth, we presume that these pigments are locally synthesized by growing feathers within the follicular tissue.

Animals↗

Increased eyelid pigmentation associated with use of latanoprost.

PURPOSE: To report increased eyelid pigmentation as an adverse side effect associated with topical latanoprost. METHOD: Case report. A 62-year-old Korean woman with normal-tension glaucoma developed bilateral increased eyelid skin pigmentation 4 months after beginning treatment with latanoprost in both eyes. Clinical examinations were performed, and external photographs were taken. RESULT: Latanoprost was discontinued. Periodic examinations revealed that the eyelid skin pigmentation gradually diminished 1 month after the cessation of the drug, and decrease in pigmentation continued over 4 months of follow-up. CONCLUSION: An increase in eyelid skin pigmentation is a possible complication of topical latanoprost therapy, and the cessation of the drug can result in loss of induced pigmentation in humans.

Antihypertensive Agents↗

Pseudohypopyon of orange pigment overlying a stable choroidal nevus.

PURPOSE: To report an unusual case of orange pigment pseudohypopyon overlying a choroidal nevus. METHODS: Observational case report. A 45-year-old man presented with best-corrected visual acuity of 20/25 and metamorphopsia in the right eye secondary to localized subfoveal fluid. The detachment displayed a peculiar appearance of layered orange pigment, like a pseudohypopyon in its inferior aspect. Closer inspection revealed an underlying choroidal nevus and no choroidal neovascular membrane. RESULTS: After 31 months of follow-up without treatment, the size of the nevus and visual acuity remained stable and metamorphopsia continued to resolve as the orange pigment and the subretinal fluid disappeared completely. CONCLUSION: An otherwise stable choroidal nevus can display overlying clumps of orange pigment and rarely massive accumulation of orange pigment in the form of a pseudohypopyon. Orange pigment pseudohypopyon can spontaneously resolve with preserved visual acuity.

Choroid Neoplasms↗

Histopathology of bone spicule pigmentation in retinitis pigmentosa.

PURPOSE: To evaluate bone spicule pigmentation, a fundus feature in retinitis pigmentosa (RP) formed by migration of pigment-containing cells to perivascular sites in the inner retina. METHODS: The authors performed light and electron microscopy, including immunocytochemistry, on the retinas from ten patients with RP and five normal donors. RESULTS: The pigment-containing cells in regions of bone spicule pigmentation were derived from the retinal pigment epithelium (RPE). The translocated cells were remarkably polarized with a number of specializations characteristic of RPE cells in situ, but they did not contain lipofuscin granules and were not immunoreactive for cellular retinaldehyde-binding protein. The cells were linked by junctional complexes and formed epithelial layers around retinal vessels and next to the inner limiting membrane. Adjacent Müller cell processes contained glial fibrillary acidic protein-positive filaments and formed microvilli and intermediate junctions, resembling those in the external limiting membrane. Vascular endothelial cells adjacent to the translocated RPE cells were thin and fenestrated, resembling the choriocapillaris, and were separated from the pigmented cells by a layer of extracellular matrix similar in organization to Bruch membrane. Thickening of the matrix layer caused narrowing and occlusion of the vascular lumina. CONCLUSIONS: The lack of lipofuscin granules and cellular retinaldehyde-binding protein immunoreactivity in the translocated RPE cells is probably related to the loss of photoreceptors. The development of fenestrations in the endothelial cells correlates with the leakiness of retinal vessels to fluorescein observed in some cases of RP. Narrowing and occlusion of vascular lumina by thickening of the surrounding layer of extracellular matrix may contribute to the loss of inner retinal neurons found in RP. These changes in the RPE, blood vessels, glia, and inner neurons warrant consideration in designing therapies to restore vision to degenerate retinas.

Adult↗

Tumors of the retinal pigment epithelium metastasize to inguinal lymph nodes and spleen in tyrosinase-related protein 1/SV40 T antigen transgenic mice.

The pigment epithelium of the retina (RPE) is derived from the optic cup and is essential for function and development of the eye. We produced a transgenic mouse line that expresses simian virus (SV40) transforming sequences under control of the 1.4 kb tyrosinase-related protein 1 (TRP-1) promoter, targeting expression of T antigen (Tag) to the RPE. In transgenic embryos, RPE cells proliferated in the anterior part of the eye and near the optic nerve. This resulted in formation of tumors, which were pigmented and of epithelial origin. In 3 months-old mice, pigmented cells were detected in spleen and inguinal lymph nodes. In spleen, tyrosinase, TRP-1 and SV40 Tag were expressed and tyrosinase was enzymatically active. Pigmented regions were positive for an epithelial marker, cytokeratin. Cell lines were established from tumor and metastases and kept in culture for more than 2 months. These were pigmented, and maintained expression of tyrosinase, TRP-1, cytokeratin and SV40 Tag. This demonstrates that RPE tumor cells metastasize to lymph node and spleen. In conclusion, the metastasis from TRP-1/Tag RPE tumors towards spleen and lymph nodes serves as potential tool to investigate biology and metastasis of tumors derived from the pigment epithelium.

Animals↗

Variations in cell density in the ganglion cell layer of the retina as a function of ocular pigmentation.

Ocular melanin regulates retinal development, including cell density gradients in the central retina, a region essential for normal visual acuity. In albinos this region is underdeveloped and peak cell numbers are reduced. It is not known whether there is a dosage relationship between pigmentation and the degree of this underdevelopment, as studies of the retinal effects of albinism have commonly used rodents. These have poorly developed central regions even in the wild type. Rabbits, however, have a unique, highly specialized, visual streak in the central retina where cell density gradients are very steep and these are reduced in albinos. Here, cell densities in the ganglion cell layer of separate groups of rabbits, with different levels of ocular pigmentation and known mutations of the tyrosinase gene coding sequence, were examined. These revealed reductions in peak cell densities and/or in the regions over which high cell densities were maintained in all hypopigmented phenotypes. There was no dosage relationship between levels of pigmentation and deficits in the ganglion cell layer as animals with relatively small reductions in retinal pigment had deficits comparable to those found in albinos. The greatest variability between pigmentation phenotypes was between the two completely unpigmented strains. Consequently, although pigment may regulate the development of the central retina, this study failed to show that it does so in a dose-dependent manner.

Animals↗

The paracrine role of stem cell factor/c-kit signaling in the activation of human melanocytes in ultraviolet-B-induced pigmentation.

The interaction of stem cell factor with its receptor, c-kit, is well known to be critical to the survival of melanocytes. Little is known about the role(s) of the stem cell factor/c-kit interaction in epidermal pigmentation, however. To clarify whether the stem cell factor/c-kit signaling has a paracrine role in ultraviolet-B-induced pigmentation, we determined whether the exposure of human keratinocytes, melanocytes, and the epidermis to ultraviolet B light stimulates the expression of stem cell factor or c-kit at the gene and/or protein levels. We further examined whether interrupting the binding of stem cell factor to c-kit by subepidermal injection of a monoclonal antibody to c-kit affects ultraviolet-B-induced pigmentation in brownish guinea pig skin. When human keratinocytes and melanocytes in culture were exposed to ultraviolet B light, transcripts of stem cell factor and c-kit (as assessed by reverse transcription polymerase chain reaction) and expression of those proteins (by enzyme-linked immunosorbent assay and western blotting) increased significantly and peaked at a dose of 20-40 mJ per cm2. In ultraviolet-B-exposed human epidermis, stem cell factor transcripts and protein expression were also markedly enhanced compared with the nonexposed epidermis. Immunohistochemistry with antibodies to stem cell factor revealed an increased staining in the ultraviolet-B-exposed epidermis, which was accompanied by a slight epidermal hyperplasia. In the course of ultraviolet-B-induced pigmentation of brownish guinea pig skin, the subepidermal injection of c-kit inhibitory antibodies completely abolished the induction of pigmentation in the ultraviolet-B-exposed area, and there was no increase in the number of dihydroxyphenylalanine-positive melanocytes. These findings indicate that the stem cell factor/c-kit signaling is critically involved in the biologic mechanism of ultraviolet-B-induced pigmentation.

Animals↗

[Pigment formation in photocoagulation lesions of the retina--biomicroscopic observations (author's transl)].

Retinal changes following photocoagulation (argon laser, xenon coagulator) were documented biomicroscopically in 31 patients who were studied prospectively for 90 days following treatment. Older photocoagulation scars were examined retrospectively in another 15 patients. The purpose of the study was to evaluate a possible new formation of pigment in the pigment epithelial layer. In most patients new pigment first appeared in the lesions two to three weeks after coagulation. The amount of pigment increased more and more slowly with time, but did not stop until the end of the observation period. Different forms of scar formation were observed, such as severe pigmentation, pigmentation outside the coagulated area, scars with glial components, but also extraretinal effects and effects on the retinal surface far from the coagulated area.

Cicatrix↗

Pigment pattern evolution by differential deployment of neural crest and post-embryonic melanophore lineages in Danio fishes.

Latent precursors or stem cells of neural crest origin are present in a variety of post-embryonic tissues. Although these cells are of biomedical interest for roles in human health and disease, their potential evolutionary significance has been underappreciated. As a first step towards elucidating the contributions of such cells to the evolution of vertebrate form, we investigated the relative roles of neural crest cells and post-embryonic latent precursors during the evolutionary diversification of adult pigment patterns in Danio fishes. These pigment patterns result from the numbers and arrangements of embryonic melanophores that are derived from embryonic neural crest cells, as well as from post-embryonic metamorphic melanophores that are derived from latent precursors of presumptive neural crest origin. In the zebrafish D. rerio, a pattern of melanophore stripes arises during the larval-to-adult transformation by the recruitment of metamorphic melanophores from latent precursors. Using a comparative approach in the context of new phylogenetic data, we show that adult pigment patterns in five additional species also arise from metamorphic melanophores, identifying this as an ancestral mode of adult pigment pattern development. By contrast, superficially similar adult stripes of D. nigrofasciatus (a sister species to D. rerio) arise by the reorganization of melanophores that differentiated at embryonic stages, with a diminished contribution from metamorphic melanophores. Genetic mosaic and molecular marker analyses reveal evolutionary changes that are extrinsic to D. nigrofasciatus melanophore lineages, including a dramatic reduction of metamorphic melanophore precursors. Finally, interspecific complementation tests identify a candidate genetic pathway for contributing to the evolutionary reduction in metamorphic melanophores and the increased contribution of early larval melanophores to D. nigrofasciatus adult pigment pattern development. These results demonstrate an important role for latent precursors in the diversification of pigment patterns across danios. More generally, differences in the deployment of post-embryonic neural crest-derived stem cells or their specified progeny may contribute substantially to the evolutionary diversification of adult form in vertebrates, particularly in species that undergo a metamorphosis.

Animals↗

Evolutionary diversification of pigment pattern in Danio fishes: differential fms dependence and stripe loss in D. albolineatus.

The developmental bases for species differences in adult phenotypes remain largely unknown. An emerging system for studying such variation is the adult pigment pattern expressed by Danio fishes. These patterns result from several classes of pigment cells including black melanophores and yellow xanthophores, which differentiate during metamorphosis from latent stem cells of presumptive neural crest origin. In the zebrafish D. rerio, alternating light and dark horizontal stripes develop, in part, owing to interactions between melanophores and cells of the xanthophore lineage that depend on the fms receptor tyrosine kinase; zebrafish fms mutants lack xanthophores and have disrupted melanophore stripes. By contrast, the closely related species D. albolineatus exhibits a uniform pattern of melanophores, and previous interspecific complementation tests identified fms as a potential contributor to this difference between species. Here, we survey additional species and demonstrate marked variation in the fms-dependence of hybrid pigment patterns, suggesting interspecific variation in the fms pathway or fms requirements during pigment pattern formation. We next examine the cellular bases for the evolutionary loss of stripes in D. albolineatus and test the simplest model to explain this transformation, a loss of fms activity in D. albolineatus relative to D. rerio. Within D. albolineatus, we demonstrate increased rates of melanophore death and decreased melanophore migration, different from wild-type D. rerio but similar to fms mutant D. rerio. Yet, we also find persistent fms expression in D. albolineatus and enhanced xanthophore development compared with wild-type D. rerio, and in stark contrast to fms mutant D. rerio. These findings exclude the simplest model in which stripe loss in D. albolineatus results from a loss of fms-dependent xanthophores and their interactions with melanophores. Rather, our results suggest an alternative model in which evolutionary changes in pigment cell interactions themselves have contributed to stripe loss, and we test this model by manipulating melanophore numbers in interspecific hybrids. Together, these data suggest evolutionary changes in the fms pathway or fms requirements, and identify changes in cellular interactions as a likely mechanism of evolutionary change in Danio pigment patterns.

Alleles↗

Development and degeneration of retina in rds mutant mice: altered disc shedding pattern in the heterozygotes and its relation to ocular pigmentation.

In the heterozygous mutant (rds/+) mice, receptor outer segments (ROS) are irregular in form and are shed as abnormally large phagosomes. In the albino rds/+ mice, peak frequency of pigment epithelial (RPE) phagosomes is higher than normal and is recorded near the end of the light period, instead of at the time of light onset as in the normal (+/+) albino mice. In pigmented mice of both genotypes, the maximum numbers of phagosomes in the RPE remain lower than in the albinos. In pigmented +/+ mice the number of phagosomes is already high at the time of light onset. The number rises to peak after one hour and then declines slowly. The lowest frequency is reached after the end of the light period. In pigmented rds/+ mice, the number of phagosomes in the RPE is lowest at the time of light onset. The number rises rapidly to peak level within two hours, then declines and remains low until light onset. If the dark period is prolonged, phagosome frequency in the rds/+ RPE remains lower than in +/+ RPE. If the light period is prolonged, phagosome frequency in the rds/+ RPE remains at a higher level than in the +/+ RPE. This differential response to altered light regimen in the rds/+ and +/+ mice is less pronounced in the pigmented than in the albino individuals. The phagosomes in the rds/+ RPE are larger than in the +/+ RPE in all light regimens. These results show that ocular pigmentation may modify the circadian pattern of ROS disc shedding in the rds/+ retina.

Animals↗

[Pigmented pemphigoid].

BACKGROUND: Pigmented bullous pemphigoid has many clinical manifestations. We report a pigmented erythematous form with disseminated bullae. CASE REPORT: A 70-year-old woman with a history of breast adenocarcinoma developed an eruption of pigmented macules on the trunk and members of 72 hour duration. At five days, there was an eruption of tight bullae. The diagnosis of bullous pemphigoid was retained because of the association of infraepidermic bullae, linear deposits of C3 along the basal membrane and the presence of the 180 kDa minor bullous pemphigoid antigen on immunoblotting. DISCUSSION: The initial pigmented aspect of this bullous pemphigoid suggested disseminated pigmented bullous erythema, but histology data with immunotransfer corrected the diagnosis. This very atypical presentation led us to look for a particular etiology. There was no argument in favor of a malignancy in this patient in complete remission after treatment of her breast adenocarcinoma. The fact that the patient was phototype IV would probably explain the pigmented nature of the initial lesions.

Aged↗

[Spectral sensitivity and visual pigments of the coastal crab Hemigrapsus sanguineus].

It has been shown that the compound eye of the coastal crab has one photosensitive pigment rhodopsin and screening pigments, black and orange one. The orange pigment has lambda max = 480 nm, rhodopsin in digitonin is stable towards hydroxylamin action, has lambda max = 490-495 nm and after bleaching is transformed into free retinene and opsin. The pigments with lambda max = 430 and 475 nm of the receptor part of the eye are also solubilized. These pigments are not photosensitive but they dissociate under the effect of hydroxylamine. The curye of spectral sensitivity of the coastal crab has the basic maximum at approximately 525 nm and the additional one at 450 nm, which seems to be provided by a combination of the visual pigment--rhodopsin (lambda max 500 nm) with a carotinoid filter (lambda max 480-490). Specific features of the visual system of coastal crab are discussed.

Animals↗

[Surface microscopy of pigmented cutaneous tumors].

BACKGROUND: Clinical guidelines for the diagnosis of pigmented lesions of the skin are not always reliable. Especially the differential diagnosis between benign dysplastic nevi (Clark's nevi) and early melanomas, as well as between melanocytic and nonmelanocytic skin tumors (seborrheic keratoses, pigmented basal cell carcinomas and angiokeratomas) is often difficult. OBJECTIVE: Surface microscopy, which is performed today under various synonyms (dermoscopy, dermatoscopy, epiluminescence microscopy, incident light microscopy, skin microscopy), has been shown to provide additional features and subtle clues for the assessment of pigmented skin lesions. METHODS: The pigmented lesions are covered in vivo with a drop of immersion oil and a glass slide, and observed in incident light by using a stereomicroscope (magnification 6- to 40-fold) or a hand-held instrument called dermatoscope (magnification 10-fold). The immersion oil renders the stratum corneum translucent and allows a better observation of distinctive alterations of the dermoepidermal junction and the papillary dermis. RESULTS: The various criteria of surface microscopy (e.g. pigment network, black dots or irregular extensions) that cannot be discerned by the naked eye are summarized and discussed in detail. The diagnostic significance but also the limitations of this technique are emphasized. CONCLUSION: Surface microscopy opens up a new dimension of clinical morphology for the diagnosis of pigmented skin tumors and facilitates a more reliable assessment of the lesions.

Angiokeratoma↗

A new model of retinal pigment epithelium transplantation with microspheres.

OBJECTIVES: To develop a 3-dimensional carrier system for subretinal transplantation of human fetal retinal pigment epithelial (HFRPE) cells and to assess their growth pattern in the rabbit subretinal space. METHODS: After a standard 3-port vitrectomy, HFRPE cells grown as microspheres on cross-linked fibrinogen were introduced into the subretinal space of rabbits. The eyes were studied at 7, 14, and 30 days after surgery by ophthalmoscopy and light microscopy. RESULTS: Ophthalmoscopically, at day 7, 11 (61%) of the 18 eyes showed radiating hyperpigmentation around the transplanted HFRPE microspheres. The results of a histological examination revealed a monolayer outgrowth of HFRPE cells, overlying host retinal pigment epithelium. The control eyes revealed a patch of chorioretinal atrophy with lymphocytic infiltration around the microspheres. CONCLUSIONS: Human fetal retinal pigment epithelial cells grown as microspheres on cross-linked fibrinogen can be successfully transplanted into the subretinal space. Cells can survive for at least 1 month and form a monolayer over the host retinal pigment epithelium cells, with a mild local inflammatory response. The difference in inflammatory responses between the eyes that underwent transplantation and the control eyes may suggest a modulating effect of the HFRPE cells on inflammation, immunity, or both. This new xenogenic model may have importance in the study of subretinal transplant cell biology and the associated immune response. CLINICAL RELEVANCE: The results of this study may be important for better understanding of the mechanisms of retinal pigment epithelium cell behavior after transplantation. The proposed model may be applicable for future clinical and experimental investigations in the area of retinal pigment epithelium transplantation.

Animals↗

Antioxidant enzymes in the aging human retinal pigment epithelium.

The antioxidant enzymes catalase and superoxide dismutase have integral roles in controlling reactive oxygen radicals that can harm cells. In the present study, we quantitated catalase activity in retinal pigment epithelium, retina, iris, and vitreous from human donors. To our knowledge, our results represent the first quantitation of catalase activity in human retinal pigment epithelium and show six-fold greater catalase activity in retinal pigment epithelium than in other ocular tissues analyzed (P less than .0001). To investigate whether aging or macular degeneration affects retinal pigment epithelium catalase or superoxide dismutase activities, we measured enzyme levels in retinal pigment epithelium from donors 50 to 90 years of age with and without evidence of macular degeneration. Superoxide dismutase activity showed no significant correlations with aging or macular degeneration, while catalase activity decreased with age (P less than .02) and macular degeneration (P less than .05) in both macular and peripheral retinal pigment epithelium.

Aged↗

Reversal of pigment gallstone disease in a canine model.

Unlike dietary-induced cholesterol gallstones, which may disappear spontaneously when the lithogenic diet is withdrawn, little is known about the natural history of pigment gallstones. We examined whether pigment gallstone disease, which can be uniformly induced in the dog by six weeks of a methionine-deficient diet, can be reversed by return to normal diet. As previously reported, all dogs develop pigment gallstones as well as significant increases in biliary total calcium, free ionized calcium, and cholesterol concentrations after six weeks of a lithogenic diet. These changes are accompanied by a significant increase in the concentration of unconjugated bile salts in bile. In addition, histologic changes in the gallbladder wall occur that are consistent with a moderate degree of chronic cholecystitis. This study clearly demonstrates that return to a normal diet for six weeks allows bile composition to normalize, gallstones to disappear in 50% of dogs, and gallbladder histologic changes to return toward normal. Thus, it would appear that pigment gallstone disease in this model may be reversible, at least early during its course. Although the relevance of these findings to pigment gallstones in humans must be established, the potential for nonoperative treatment of pigment gallstones should not be discounted.

Animals↗

Structure and developmental expression of the ascidian TRP gene: insights into the evolution of pigment cell-specific gene expression.

The tyrosinase family in vertebrates consists of three related melanogenic enzymes: tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2. These proteins control melanin production in pigment cells and play a crucial role in determining vertebrate coloration. We have isolated a gene from the ascidian Halocynthia roretzi which encodes a tyrosinase-related protein (HrTRP) with 45-49% identity with vertebrate TRP-1 and TRP-2. The expression of the HrTRP gene in pigment lineage a8.25 cells starts at the early-mid gastrula stage, which coincides with the stage when these cells are determined as pigment precursor cells; therefore, it provides the earliest pigment lineage-specific marker, which enables us to trace the complete cell lineage leading to two pigment cells in the larval brain. In addition, the expression pattern of the HrTRP gene appears to share similar characteristics with the mouse TRP-2 gene although structurally the HrTRP gene is more closely related to mammalian TRP-1 genes. Based on these observations and on results from molecular phylogenetic and hybridization analyses, we suggest that triplication of the tyrosinase family occurred during the early radiation of chordates. Initially, duplication of an ancestral tyrosinase gene produced a single TRP gene before the urochordate and cephalochordate-vertebrate divergence, and a subsequent duplication of the ancestral TRP gene in the vertebrate lineage gave rise to two TRP genes before the emergence of teleost fishes. Evolution of the melanin synthetic pathway and possible phylogenetic relationships among chordate pigment cells that accommodate the metabolic process are discussed. Dev Dyn 1999;215:225-237.

Amino Acid Sequence↗