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PubMed1989

Retinomotor movements in the frog retinal pigment epithelium: dependence of pigment migration on Na+ and Ca2+.

The ionic dependence of the screening-pigment migrations in the frog retinal epithelium (RPE) was quantitatively studied with eyecups incubated in media of different compositions. Typical migrations in response to light and darkness, equivalent to those observed in the intact animal, were fully accomplished and maintained for up to 6 hr by the isolated organ bathed in Ringer solution rich with O2. Pigment migration in either direction was completed under the appropriate illumination conditions at any time during the day, indicating that circadian influences, if present in the intact animal, can be overridden in the isolated organ by light or darkness alone. Pigment aggregation toward the dark-adapted position was inhibited by: (a) low external Ca2+, (b) high external Na+, and (c) drugs expected to increase the cytoplasmic levels of either Na+, or Ca2+, like ouabain, caffeine and the ionophore A23187. However, the inhibition caused by low Ca2+ did not occur if Na+ was also reduced in the incubation medium. On the other hand, an increase in the concentration of external Ca2+ or the addition of Co2+ to the normal Ringer facilitated pigment aggregation in the dark. Pigment dispersion to the light-adapted position was unaffected by any of the above conditions. This is the first report of full and stable pigment responses in the RPE of vertebrate eyes incubated under simple physiological conditions. The results seem to conciliate a discrepancy of previous reports on the Ca2+ dependence of RPE movements, and are compatible with current views on ionic mechanisms in analogous systems of intracellular transport.

Adaptation, Ocular↗
PubMed1989

Role of microtubules in pigment granule migration in teleost retinal pigment epithelial cells.

In cells of the teleost retinal pigment epithelium (RPE), melanin pigment granules migrate in response to changes in environmental light conditions. Melanin granules disperse into the RPE cell's long apical projections in response to the onset of light, and aggregate towards the base of the RPE cell in response to the onset of darkness. The RPE cells possess numerous microtubules and actin filaments, which in the apical projections are aligned longitudinally. Previous cytochalasin studies have shown that intact actin filaments are required for pigment granule dispersion and maintenance of the dispersed state (Burnside, Adler and O'Connor (1983). Invest. Ophthalmol. Vis. Sci. 24, 1). We report here that pigment granule aggregation is strongly inhibited when the highly stable microtubules of RPE apical projections are disrupted by a combination of cold and nocodazole treatments. Pigment dispersion and maintenance of the dispersed and aggregated states are unaffected by microtubule disruption. These results indicate that microtubules are required for RPE pigment aggregation but not for dispersion.

Animals↗
PubMed1998

The eyes of deep-sea fish. I: Lens pigmentation, tapeta and visual pigments.

Deep-sea fish, defined as those living below 200 m, inhabit a most unusual photic environment, being exposed to two sources of visible radiation; very dim downwelling sunlight and bioluminescence, both of which are, in most cases, maximal at wavelengths around 450-500 nm. This paper summarises the reflective properties of the ocular tapeta often found in these animals, the pigmentation of their lenses and the absorption characteristics of their visual pigments. Deep-sea tapeta usually appear blue to the human observer, reflecting mainly shortwave radiation. However, reflection in other parts of the spectrum is not uncommon and uneven tapetal distribution across the retina is widespread. Perhaps surprisingly, given the fact that they live in a photon limited environment, the lenses of some deep-sea teleosts are bright yellow, absorbing much of the shortwave part of the spectrum. Such lenses contain a variety of biochemically distinct pigments which most likely serve to enhance the visibility of bioluminescent signals. Of the 195 different visual pigments characterised by either detergent extract or microspectrophotometry in the retinae of deep-sea fishes, ca. 87% have peak absorbances within the range 468-494 nm. Modelling shows that this is most likely an adaptation for the detection of bioluminescence. Around 13% of deep-sea fish have retinae containing more than one visual pigment. Of these, we highlight three genera of stomiid dragonfishes, which uniquely produce far red bioluminescence from suborbital photophores. Using a combination of longwave-shifted visual pigments and in one species (Malacosteus niger) a chlorophyll-related photosensitizer, these fish have evolved extreme red sensitivity enabling them to see their own bioluminescence and giving them a private spectral waveband invisible to other inhabitants of the deep-ocean.

Animals↗
PubMed1998

Long-term studies on allotransplantation of rabbit retinal pigment epithelial cells double-labelled with 5-bromodeoxyuridine and natural pigment.

OBJECTIVE: To facilitate the identification of transplanted retinal pigment epithelial (RPE) cells, we sought to double-label the cells with 5-bromodeoxyuridine (BrdU) and with natural pigment. The BrdU is not lost during cell division but does require immunohistochemical methods for visualization; the pigment on the other hand, allows immediate, obvious identification, but is gradually lost with cell division. Together they provide a convenient, long-term double label. METHODS: Non-confluent RPE cells at the second to the fifth passages were labelled with 5-BrdU and pigment. The double-labelled RPE cells were transplanted onto Bruch's membrane of 72 eyes of New Zealand albino rabbits. The labelled cells were localized by anti-BrdU antibody and the avidin biotin-alkaline phosphatase complex (ABC-AP) method, and by visible inclusions of pigment. RESULTS: The transplanted RPE cells had distinct basal and apical morphology, and were in close contact with the photoreceptor outer segments of the host. The BrdU label was restricted to the nuclei of the RPE cells, which were stained blue. The pigment was located in the cytoplasm of the apical portion of these RPE cells. No evidence of severe rejection was seen. CONCLUSIONS: Using this double-label method, transplanted RPE cells could be readily and reliably identified till one year after transplantation. The transplanted RPE cells revealed normal morphology with some function: they had distinct basal and apical morphology as seen in close contact with the outer segment of photoreceptor cells. The junctional complexes were well formed with neighboring RPE cells. The transplanted RPE cells phagocytose shed outer segments of the host. No evidence of rejection was observed, suggesting that the subretinal space of the rabbit may possess some degree of immunologic privilege. This experiment provides reliable evidence for the clinical research of allotransplantation of RPE cells.

Affinity Labels↗
PubMed2003

[Retinal pigment epithelial atrophic tracks secondary to central serous pigment epitheliopathy].

PURPOSE AND METHODS: We report the cases of three patients with retinal pigment epithelial atrophic tracks secondary to central serous pigment epitheliopathy specially focusing on fluorescein angiographic findings. This entity is considered an atipical manifestation of central serous chorioretinopathy called chronic diffuse retinal pigment epitheliopathy. RESULTS AND CONCLUSIONS: We have studied 69 patients with the diagnose of central serous pigment epiteliopathy in our unit; 10.14% manifested diffuse retinal pigment epitheliopathy and 5.79% showed retinal pigment epithelial atrophic tracks. Both eyes were involved in 100% and all of them were males with a median age of 53.33 years. We can conclude that this entity usually affects adult males and it is frequently bilateral.

Fluorescein Angiography↗
PubMed1987

Fine structural significance of bone corpuscle-shaped pigmentation in the human retinal pigment degeneration.

Two cases of advanced RPD were observed their trypsin digested vascular trees and retinal substructures, especially RPE and pigmented cells in the neural retina. In the both eyes the visual cell was almost completely degenerated to disappear except posterior regions and apical part of RPE came to contact with neural retina or external limiting membrane formed by tight junction between adjacent Müller cell processes. Occasionally RPE in the equatorial region had completely disappeared and was replaced by Müller cell processes which was directly apposed to the Bruch's membrane. Pigmented cells were observed at almost all levels of the neural retina and along the intraretinal capillary. Pigmented cells were classified into three types. The first type of the cell was corresponded with the macrophage in the substructural features. The second type of the cell was RPE proliferated or migrated into the neural retina forming bone corpuscle-shape pigmentation in the retina and along the intraretinal capillary. Müller cell processes also indicated up-taking pigment granules, that is, the third type of the pigmented cell.

Adult↗
PubMed1987

Mucocutaneous pigmented spots and oral myxomas: the oral manifestations of the complex of myxomas, spotty pigmentation, and endocrine overactivity.

The complex of myxomas, spotty pigmentation, and endocrine overactivity is a recently recognized syndrome, transmitted as an autosomal dominant trait. The most serious component of the disorder is cardiac myxoma, which has caused the death of one fourth of the affected patients and serious disability in an equal number. It is, therefore, important to recognize patients at risk from the syndrome and, in particular, to test them for cardiac myxoma. Fortunately, in many patients the myxoma complex has a clearly visible marker: mucocutaneous pigmentation. Among 58 patients with the syndrome, spotty facial pigmentation was present in 36 (62%), and 29 (50%) of these also had pigmented spots on their lips. This type and distribution of pigmentation should be a clue to the possible presence of the complex of myxomas, spotty pigmentation, and endocrine overactivity, and patients thus affected should be referred for further investigation. Oral cavity myxoma(s) occurred in four patients with the syndrome.

Adult↗
PubMed1975

The occurrence of actinlike filaments in association with migrating pigment granules in frog retinal pigment epithelium.

In the retina of the frog and certain other animals, melanin pigment granules move in response to light so as to shield photoreceptor outer segments. The granules are contained within the cells of the pigment epithelium (PE) which lie as a continuous sheet between the neural retina and the choroid. Moderate illumination of the eye causes the melanin granules to move from a region within a PE cell body into numerous fingerlike extensions of the cell which interdigitate with the receptor outer segments. This migration takes many minutes and is reversed when the light falling on the eye increases in intensity. Several reviews are concerned with the early descriptions of this phenomenon (6,30) and with more recent experiments (1,5,19). The mechanism of the pigment granule motion is undetermined although there are studies concerning PE ultrastructure (8, 23, 31), scanning electron microscopy of the fingerlike extensions of the PE cells (27), the role of the PE in photoreceptor phagocytosis (32), the nature of the pigment granules (19), and the action spectrum of the light which induces the migration (16). This study reports the presence of a system of microfilaments associated with the pigment granules in the fingerlike extensions processes of the PE cells. We demonstrate by heavy meromyosin (HMM) labeling that the filaments are actinlike in character and suggest that these filaments could be responsible for the migration of the melanin pigment granules.

Actins↗
PubMed2002

Prevalence of pigmented lens striae in a black population: a potential indicator of age-related pigment dispersal in the anterior segment.

PURPOSE: To determine the prevalence of pigmented striae of the anterior lens capsule, with or without associated glaucoma, in a black primary eye care population. METHODS: Over a 16-month period, five practitioners searched for pigmented lens striae (PLS) among consecutive patients who underwent pupillary dilation during routine eye care provided within the primary care service of an urban eye clinic in Chicago, Illinois. RESULTS: Meeting the inclusion criteria were 1608 blacks (mean age +/- SD, 40.9 +/- 23.7 years; range, 5 to 100; 1056 females, 552 males). Among the group, 29 (1.8%) subjects had PLS (mean age, 66.5 +/- 11.3 years; range, 33 to 88; 25 females, 4 males). PLS were bilateral 89% of the time. Sixteen of the 29 (55%) blacks had central corneal endothelial pigment dusting (14 bilateral), frequently creating a well-formed Krukenberg's spindle. Trabecular pigmentation varied among the PLS subjects from mild to heavy. Using multiple logistic regression, age (in years) (odds ratio, 1.05; 95% confidence interval, 1.02 to 1.07; p = 0.0003), female gender (odds ratio, 4.46; 95% confidence interval; 1.03 to 19.19; p = 0.045), and hyperopic refractive error (in diopters) (odds ratio, 1.35; 95% confidence interval; 1.09 to 1.67; p = 0.006) were significant predictors of PLS. CONCLUSIONS: PLS were present in about 1.8% (2.4% females, 0.7% males) of our black population, and they were frequently associated with other signs of intraocular pigment dispersion. Age, female gender, and refractive error were significant predictors for PLS. This is new information that is helpful for understanding a clinical sign that may be an indicator of age-related pigment dispersal within the anterior segment.

Adolescent↗
PubMed2005

Altered melanocyte differentiation and retinal pigmented epithelium transdifferentiation induced by Mash1 expression in pigment cell precursors.

Transcription factor genes governing pigment cell development that are associated with spotting mutations in mice include members of several structural transcription factor classes but not members of the basic helix-loop-helix (bHLH) class, important for neurogenesis and myogenesis. To determine the effects of bHLH factor expression on pigment cell development, the neurogenic bHLH factor Mash1 was expressed early in pigment cell development in transgenic mice from the dopachrome tautomerase (Dct) promoter. Dct:Mash1 transgenic founders exhibit variable microphthalmia and patchy coat color hypopigmentation. Transgenic F1 mice exhibit microphthalmia with complete coat color dilution. Marker analysis demonstrates that Mash1 expression in the retinal pigmented epithelium (RPE) initiates neurogenesis in this cell layer, whereas expression in remaining neural crest-derived melanocytes alters their differentiation, in part by profoundly downregulating expression of the p (pink-eyed dilution) gene, while maintaining their cell fate. The effects of transcriptional perturbation of pigment cell precursors by Mash1 further highlight differences between pigment cells of distinct developmental origins, and suggest a mechanism for the alteration of melanogenesis to result in marked coat color dilution.

Animals↗
PubMed1983

Co-cultivation of retinoblastoma with fibroblasts, iris pigment epithelium, and retinal pigment epithelium in tissue culture.

Retinoblastoma cells of the Y79 line were co-cultivated with human fibroblasts and bovine iris and retinal pigment epithelium in tissue culture. The Y79 cells, which characteristically grow as a suspension culture, were found to attach directly to the fibroblasts and pigment epithelium on the flask surface. Electron microscopic examination of the fibroblast-retinoblastoma co-cultures revealed numerous pinocytotic vesicles lining the fibroblast cell borders that were in contact with the tumor cells. The retinoblastoma cells contained increased numbers of ribosomes, endoplasmic reticulum, and-mitochondria. Fibroblastic processes appeared to wrap around and engulf tumor cells. In both the iris and retinal pigment epithelium co-cultures with retinoblastoma cells, there were increased numbers of mitochondria in the tumor cells in areas adjacent to pigment epithelium but no pinocytotic vesicles were seen. The pigment epithelium attached to Y79 cells showed fewer processes than did the fibroblasts in co-culture. In summary, both fibroblast and pigment epithelium functioned as an effective carrier cell layer for retinoblastoma cells. In addition, we believe that the fibroblast layer removed substances secreted by the tumor cells via pinocytotic vesicles.

Animals↗
PubMed1993

Dietary restriction slows age pigment accumulation in the retinal pigment epithelium.

PURPOSE: The accumulation of age pigment, or lipofuscin, in postmitotic cells appears to be a universal feature of the aging process in animals. In mammals, the lipofuscin content of the retinal pigment epithelium (RPE) increases progressively during senescence. Dietary restriction has been shown to slow the rate at which many biologic parameters change during aging. Experiments were conducted to determine if dietary restriction alters the rate of age pigment accumulation in the RPE. METHODS: Male Wistar rats were placed on one of three dietary regimens starting at weaning. One group was fed a nutritionally complete diet ad libitum. Another group was fed the same diet but was only allowed to consume 60% as much food daily as the ad libitum group ate. The final group was fed ad libitum a nutritionally complete diet that had a lower caloric density per gram than the diets fed to the other animals primarily because of the replacement of carbohydrate with oat fiber. Ultrastructural morphometric analysis was used to determine the RPE age pigment content in the first group at 6 months of age, and in all of the groups at 18 months of age. RESULTS: Dietary restriction, achieved either by reducing total food intake or by reducing the caloric content of the diet, resulted in significant decreases in RPE lipofuscin accumulation. CONCLUSIONS: Dietary restriction provides a relatively simple means by which RPE age pigment content can be modulated. This should prove useful in assessing the role of RPE lipofuscin accumulation in age-related retinal disorders. That the oat fiber diet fed ad libitum was almost as effective as restriction of total food intake in slowing RPE age pigment accumulation indicates that the effect of restricted caloric intake is not mediated by almost constant hunger.

Aging↗
PubMed1987

In vivo epiluminescence microscopy of pigmented skin lesions. II. Diagnosis of small pigmented skin lesions and early detection of malignant melanoma.

Pattern analysis by epiluminescence microscopy of pigmented skin lesions was tested in a study of 318 small pigmented skin lesions that were diagnostically equivocal when examined with the naked eye. An improvement of clinical diagnosis was achieved by epiluminescence microscopy for practically all lesions, both benign and malignant, and was equally impressive for melanocytic and nonmelanocytic lesions. Improvement in diagnostic accuracy was as follows: for small nodular melanomas, from 50% to 70%; for superficial spreading melanoma in situ, from 46% to 80%; for invasive superficial spreading melanoma, from 64% to 90%; and for early lentigo maligna and lentigo maligna melanoma, from 67% to 88%. Conversely, the diagnosis of pigmented Spitz nevi improved from 46% to 93% and of pigmented basal cell carcinomas from 60% to 90%, which appears equally important because most of these lesions had clinically been considered to represent melanomas. The use of epiluminescence microscopy also resulted in considerable improvement in the diagnosis of dysplastic nevi, which was particularly helpful in making therapeutic decisions. Epiluminescence microscopy greatly expands the diagnostic armamentarium available for pigmented skin lesions at a clinical level and thus increases the chances of detecting or ruling out melanoma in its earliest stages.

Basal Cell Carcinoma↗
PubMed2003

Extensive pigmented villonodular synovitis with markedly pigmented lymphadenopathy and its implication for differential diagnosis with malignant melanoma.

A 51-year-old male presented with a 5 cm left knee mass. Fine needle aspiration revealed large epithelioid cells with prominent nucleoli and abundant cytoplasmic pigment, consistent with malignant melanoma. Left inguinal lymphadenopathy was present, which was suspicious for metastatic disease by ultrasound examination. A dark perianal skin lesion was also identified, therefore raising the possibility of a primary melanoma. The knee and perianal lesions were resected and inguinal sentinel node biopsy was performed. In the specimen from the knee, there were clusters and fascicles of spindle and epithelioid cells with prominent nucleoli. Many of the cells displayed abundant, granular, brown, cytoplasmic pigment. The lymph node showed clusters of similar cells located in the subcapsular sinus. Immunohistochemical study showed that the cells expressed CD68, but failed to express S-100, MART-1, and gp100. The cytoplasmic pigment was positive for iron staining. The final diagnosis was pigmented villonodular synovitis. This case illustrates that pigmented villonodular synovitis may present with lymphadenopathy, mimicking a malignant process, including melanoma. Immunohistochemical studies may be essential for establishing the correct diagnosis.

Biopsy, Fine-Needle↗
PubMed2006

Pigment pattern formation in the quail mutant of the silkworm, Bombyx mori: parallel increase of pteridine biosynthesis and pigmentation of melanin and ommochromes.

The larval pigment pattern in the silkworm, Bombyx mori, is formed by melanin, ommochromes and pteridines. During development all these pigments are synthesized autonomously, and possibly also with mutual interaction between them, to yield unique pigment patterns. In order to find the key trigger for such pigment pattern formation, developmental changes in pteridine biosynthesis were studied using the quail mutant (q/q), which has darker larval marks formed by melanin and an abundance of ommochromes in the integument. In the current study, emphasis has been placed on the analysis of GTP-cyclohydrolase I (GTP-CH I), which is a key enzyme for the biosynthesis of pteridines, during the development of the silkworm. Results of Northern blotting showed that in the quail mutant strong signals of GTP-CH I mRNA appeared around each period of ecdysis, while no such signals appeared in the background strain (+q/q) used. Also, both GTP-CH I activities and pteridine content were higher in the quail mutant compared with the background strain. These results strongly suggest that pteridine biosynthesis is closely linked to the formation of melanin and ommochromes. It is also suggested here that in the silkworm a recessive gene (q) may be involved in the regulation of its pigment pattern formation.

Alcohol Oxidoreductases↗
PubMed1980

Orientation of pigments and pigment-protein complexes in the green photosynthetic bacterium Prosthecochloris aestuarii.

The orientation of pigments and pigment-protein complexes of the green photosynthetic bacterium Prosthecochloris aestuarii was studied by measurement of linear dichroism spectra at 295 and 100 K. Orientation of intact cells and membrane vesicles (Complex I) was obtained by drying on a glass plate. The photochemically active pigment-protein complexes (photosystem-protein complex and reaction center pigment-protein complex) and the antenna bacteriochlorophyll a protein were oriented by pressing a polyacrylamide gel. The data indicate that the near-infrared transitions (Qy) of bacteriochlorophyll c and most bacteriochlorophyll a molecules have a relatively parallel orientation to the membrane, whereas the Qy transitions of the bacteriochlorophyll a in the antenna protein are oriented predominantly perpendicularly to the membrane. Carotenoids and the Qx transitions (590-620 nm) of bacteriochlorophyll a, not belonging to the bacteriochlorophyll a protein, have a relatively perpendicular orientation to the membrane. The absorption and linear dichroism spectra indicate the existence of different pools of bacteriochlorophyll c in the chlorosomes and of carotenoid and bacteriopheophytin c in the cell membrane. The results suggest that the photosystem-protein and reaction center pigment-protein complexes are oriented with their short axes approximately perpendicular to the plane of the membrane. The symmetry axis of the bacteriochlorophyll a protein has an approximately perpendicular orientation.

Bacterial Proteins↗
PubMed1994

Reduction of DNA synthesis, pigment synthesis, pigmentation gene mRNA and resistance to UVB in human melanoma cells treated with analogues of a histamine (H2) agonist.

Two groups of S-[2-(N,N-dialkylamino)ethyl]isothiourea derivates which depigmented melanoma cells either with inhibition of tyrosinase (group 1, R = methyl, isopropyl) or without inhibition of tyrosinase (group 2, R = benzyl, phenyl) were studied. Treatment of human melanoma cells with non-lethal doses of group 1 drugs led to a reduction in the levels of mRNA for the pigmentation genes tyrosinase, tyrosinase-related protein-1 and Pmel 17. The group 1 drug S-[2-N,N-diisopropylamino)ethyl[isothiourea] (DINOR) (R = isopropyl) produced only moderate inhibition of DNA, RNA and protein synthesis in three cell lines during the first 24 hr of treatment, and there was no correlation between the extent of inhibition and long-term toxicity. A group 2 drug (R = benzyl) rapidly inhibited DNA synthesis in an amelanotic melanoma cell line (MM96E) sensitive to killing by the drug; association of the latter with inhibition of RNA or protein synthesis was less clear. MM96E cells were also sensitive to killing by reactive oxygen species. In pigmented melanoma cells (MM418), incorporation of [125I]thiouracil, a false precursor of melanin, increased during the first 24 hr of treatment with DINOR whereas a group 2 drug (R = phenyl) inhibited incorporation of [125I]thiouracil. Cells depigmented by treatment with drugs from either group suffered the same amount of DNA damage as pigmented cells after UVB irradiation, as judged by inhibition of DNA synthesis, but did not recover as well as pigmented cells, whether or not drug was present during recovery. The results suggested that (1) group 1 agents down-regulated message for several pigmentation genes, possibly at the transcriptional level; (2) the toxicity of group 2 drugs was related to reactive oxygen species; and (3) melanin protected cells from UVB by enhancing cellular recovery.

Blotting, Northern↗
PubMed2003

Changes in the energy distribution between chlorophyll-protein complexes of thylakoid membranes from pea mutants with modified pigment content. I. Changes due to the modified pigment content.

The low-temperature (77 K) emission and excitation chlorophyll fluorescence spectra in thylakoid membranes isolated from pea mutants were investigated. The mutants have modified pigment content, structural organization, different surface electric properties and functions [Dobrikova et al., Photosynth. Res. 65 (2000) 165]. The emission spectra of thylakoid membranes were decomposed into bands belonging to the main pigment protein complexes. By an integration of the areas under them, the changes in the energy distribution between the two photosystems as well as within each one of them were estimated. It was shown that the excitation energy flow to the light harvesting, core antenna and RC complexes of photosystem II increases with the total amount of pigments in the mutants, relative to the that to photosystem I complexes. A reduction of the fluorescence ratio between aggregated trimers of LHC II and its trimeric and monomeric forms with the increase of the pigment content (chlorophyll a, chlorophyll b, and lutein) was observed. This implies that the closer packing in the complexes with a higher extent of aggregation regulates the energy distribution to the PS II core antenna and reaction centers complexes. Based on the reduced energy flow to PS II, i.e., the relative increased energy flow to PS I, we hypothesize that aggregation of LHC II switches the energy flow toward LHC I. These results suggest an additive regulatory mechanism, which redistributes the excitation energy between the two photosystems and operates at non-excess light intensities but at reduced pigment content.

Chlorophyll↗