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PubMed2001

Anterior chamber angle anomalies associated with signs of pigment dispersion in a group of black probands and their first-degree relatives.

PURPOSE: To evaluate the presence of iridocorneal angle anomalies associated with signs of pigment dispersion among a group of black probands and their first-degree relatives. METHODS: Eleven blacks who exhibited pigment dispersion syndrome (PDS) signs, including Krukenberg's spindles, moderate-to-heavy trabecular meshwork pigmentation, and peripheral lenticular/zonular pigmentation, received a complete eye examination that included gonioscopy. Overt iridocorneal angle abnormalities other than pigment deposition were photo-documented. Twenty-two first-degree relatives (6 siblings, 15 children, and 1 parent) of these probands underwent similar examination. RESULTS: Among the subjects, 5 of 11 probands (age range 13 to 59 years) and 4 of 22 relatives (age range 14 to 51 years) exhibited definite angle anomalies. The nine subjects with angle anomalies belonged to 7 of 11 separate families. The four relatives with angle anomalies did not have PDS according to our criteria, but two other relatives from two additional families did have signs consistent with clinical PDS. Types of angle anomalies included (1) peripheral anterior synechia-like lesions; (2) a prominent concavity of the peripheral iris at the 6-o'clock meridian; (3) a whitish, thread-like band of tissue near the iris base; (4) a prominent, externally-visible Schwalbe's line at the 6-o'clock meridian; and (5) a prominent, web-like confluence of exaggerated iris processes 360 degrees along the angle wall. Iris processes and prominent Schwalbe's lines were not considered abnormal or anomalous unless they were clearly atypical. CONCLUSIONS: Iridocorneal angle anomalies, other than pigment deposition, were common among our black group who exhibited signs of pigment dispersion as well as among their first-degree relatives. Further consideration should be given to the possibility that among some patient groups, overt goniodysgenesis could be part of a constellation of signs indicative of a pigment dispersion syndrome. Potentially, clinically detectable goniodysgenesis could prove to be a useful marker to identify certain subjects who carry PDS genetic traits but who have not expressed complete phenotypical disease.

Adolescent↗
PubMed2001

Keratometry and axial length in pigment dispersion syndrome: a descriptive case-control study.

PURPOSE: Pigment dispersion syndrome and pigmentary glaucoma are characterized by loss of pigment from the posterior surface of the iris due to reverse pupillary block. This may be due to an anomalous relation between the position of the globe within the orbit, the axial length of the globe, and the corneal curvature. The authors compared axial length, keratometry, and exophthalmometry in patients with pigment dispersion syndrome and pigmentary glaucoma and in healthy controls. METHODS: Thirteen pigment dispersion syndrome and pigmentary glaucoma and 17 controls underwent refraction, keratometry, A-scan and exophthalmometry. Patients with pigment dispersion syndrome and pigmentary glaucoma were selected in a university glaucoma practice, and controls were selected for their age and refraction from the staff of the hospital. Both groups were comparable in age and refraction. RESULTS: Mean age of pigment dispersion syndrome patients and healthy controls was 46.54 and 41.82 years (P = 0.30), respectively, and mean refraction (spherical equivalent) was -4.53 and -4.32 diopters, (P = 0.84), respectively. No statistical differences were noted in axial length measured with A-scan (25.98 and 25.14, P = 0. 15) or anterior chamber depth and lens thickness. The pigment dispersion syndrome and pigmentary glaucoma group had flatter keratometry than the myopic controls. Mean keratometry was 42.39 +/- 1.77 and 44.34 +/- 1.50 (P = 0.003), respectively. CONCLUSION: The results show that patients with pigment dispersion syndrome have flatter keratometry of approximately 2 diopters compared with age-matched myopic controls. This finding suggests a difference in architecture of the anterior segment.

Adult↗
PubMed1990

10,20-Methanorhodopsins: (7E,9E,13E)-10,20-methanorhodopsin and (7E,9Z,13Z)-10,20-methanorhodopsin. 11-cis-locked rhodopsin analog pigments with unusual thermal and photo-stability.

Synthesis of the retinal analog, 10,20-methanoretinal (R6), where the 11Z conformation is locked in a six-membered ring, yielded four stereoisomers (7E,9E,13E, 7E,9E,13Z, 7E,9Z,13E and 7E,9Z,13Z). These four isomers were separated by straight-phase isocratic HPLC and identified by 1H-NMR and NOE analysis. All isomers smoothly recombined with bovine opsin at a relatively high rate (5-10% of that of the natural chromophore 11Z-retinal). The corresponding 13E and 13Z isomers yielded identical analog pigments, probably due to rapid thermal isomerization around the C13 = C14 double bond. The (7E,9E)-isomers produced a pigment with maximal absorbance at 510 nm, while the pigment produced from the (7E,9Z)-isomers had maximal absorbance at 494 nm. Based upon kinetic considerations, the chromophore structure in the 510-nm-absorbing pigment should be (7E,9E,13E), i.e. equivalent to 11Z-retinal and rhodopsin, while the chromophore structure in the 494-nm-absorbing pigment should be (7E,9Z,13Z), i.e. equivalent to (9Z,11Z,13Z)-rhodopsin, an isorhodopsin analog. In analogy to the 11-cis-locked rhodopsin analogs Rh5 and Rh7, the 510-nm-absorbing pigment, (7E,9E,13E)-10,20-methanorhodopsin, was dubbed Rh6 and the 494-nm-absorbing pigment. (7E,9Z,13Z)-10,20-methanorhodopsin, was dubbed Iso6. The opsin shift of Rh6 (2660 cm-1) is practically identical to that of rhodopsin itself (2650 cm-1). Rh6 and Iso6 are nearly as stable as rhodopsin towards hydroxylamine and solubilization in detergent solution and could be easily purified and reconstituted into proteoliposomes by established procedures. Due to the 11-cis-lock, Rh6 is much less photolabile (bleaching rate less than 1%) than rhodopsin, but it is not completely photostable, probably since photoisomerization around the C7 = C8, C9 = C10 and C13 = C14 bonds is allowed. Illumination of either Rh6 or Iso6 does not generate the common photointermediates but instead produces a complex pattern of photochemical transitions, which during continuous illumination leads to the same final steady state, absorbing at 498 nm. This process is accompanied by a slow but steady loss of pigment, probably due to hydrolytic release of chromophore, which is markedly accelerated in the presence of hydroxylamine. In a physiological assay (light-dependent activation of rod cGMP phosphodiesterase) Rh6 is only marginally active and this probably reflects conformational changes accompanying the above-mentioned photochemical transitions. This supports the concept that normal rhodopsin-based phototransduction requires 11Z to all-E isomerization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

510-nm pigmented lesion dye laser. Its characteristics and clinical uses.

BACKGROUND: Benign pigmented lesions are of a cosmetic concern to many individuals. Numerous treatments exist, including several types of lasers. The Candela 510 nm pigmented lesion dye laser has recently been added to this armamentarium. It is designed specifically for the treatment of superficial pigmented lesions while significantly decreasing the risk of scarring and prolonged hypopigmentation. OBJECTIVES: To describe the characteristics of the Candela pigmented lesion dye laser and report on the therapeutic outcome of patients treated for actinic lentigines, café-au-lait macules, melasma and red tattoos by one of the authors (RCG). METHODS: The Candela 510 nm pigmented lesion dye laser was used to treat solar lentigines, café-au-lait macules, melasma and red tattoo. RESULTS: Excellent outcomes resulted on facial and hand lentigines (89% and 88% of patients had greater than 75% clearing, respectively), but often required more than one treatment. Lentigines located on the upper extremities and trunk improved less dramatically. Immediate greying occurred universally. Bruising was often noted. Treatment failures have been observed especially in treating lentigines located on the lower extremities. Café-au-lait macules responded inconsistently, with facial lesions giving the best results. Melasma responded poorly, often with hyperpigmentation. Three red tattoos cleared. Treatment failure may be related to inaccurate clinical assessment of pigment depth or regrowth of the lesion. Several cases are presented to demonstrate clinical and histologic effects of the laser. CONCLUSION: The Candela 510-nm pigmented lesion dye laser is an effective treatment for superficial pigmented lesions. Its associated morbidity is minimal.

Adult↗
PubMed1991

Ring oxidized retinals form unusual bacteriorhodopsin analogue pigments.

Three ring oxidized retinal analogues have been isolated from the exhaustive oxidation of all-trans retinal. All-trans 4-oxoretinal and 2,3-dehydro-4-oxoretinal have similar absorption maxima to that of all-trans retinal and have been shown to be in the 6-s-cis conformation in solution. Pigments formed with bacterioopsin exhibit absorption maxima (520 nm) blue-shifted from that of bacteriorhodopsin (bR), indicating a disturbance of the external point charge by the electronegative carbonyl moiety at the 4 position. The third analogue contains a ring contracted to a cyclopentenyl-alpha,beta-dione. Unlike the majority of retinals, this analogue displays a 6-s-trans conformation in solution and has a red-shifted absorption maximum at 435 nm. The resulting bR analogue pigment (515 nm) is formed five times faster than the other oxoretinal pigments. All three oxoretinal pigments show an irreversible 20 nm blue shift upon exposure to white light. The 4-oxo and 2,3-dehydro-4-oxoretinal pigments, after irradiation, undergo a small reversible blue shift (4-8 nm) on dark adaptation. These two pigments pump protons, although with slowed photocycle kinetics, demonstrating that these structural changes (addition of the carbonyl at the C-4 and insertion of a double bond in the ring) do not block the function of the pigment. Extraction of the C-15 tritiated analogue retinals from illuminated and non-illuminated pigments of all three oxoretinals yield identical results. Therefore, any crosslinking of these oxoretinals to the protein is by linkages which are unstable to the extraction procedures.

Bacteriorhodopsins↗
PubMed1993

Pigment complexes of light-harvesting chlorophyll a/b binding protein are stabilized by a segment in the carboxyterminal hydrophilic domain of the protein.

In order to identify segments of light-harvesting chlorophyll a/b-binding protein (LHCP) that are important for pigment binding, we have tested various LHCP mutants regarding their ability to form stable pigment-protein complexes in an in vitro reconstitution assay. Deletion of 10 C-terminal amino acids in the LHCP precursor, pLHCP, did not significantly affect pigment binding, whereas deletion of one additional amino acid, a tryptophan, completely abolished the formation of stable pigment-protein complexes. This tryptophan, however, can be exchanged with other amino acids in full-length pLHCP without noticeably altering the stability or spectroscopic properties of pigment complexes made with these mutants. Thus, the tryptophan residue is not likely to be involved in a highly specific interaction stabilizing the complex. A double mutant of LHCP lacking 66 N-terminal and 6 C-terminal amino acids still forms pigmented complexes that are virtually identical to those formed with the full-length protein concerning their pigment composition and spectroscopic properties. We conclude that about 30% of the polypeptide chain in LHCP is not involved in pigment binding.

Amino Acid Sequence↗
PubMed1984

Pigment Production from Immobilized Monascus sp. Utilizing Polymeric Resin Adsorption.

Pigment production by the fungus Monascus sp. was studied to determine why Monascus sp. provides more pigment in solid culture than in submerged culture. Adding a sterilized nonionic polymeric adsorbent resin directly to the growing submerged culture did not enhance the pigment production, thus indicating that pigment extraction is probably not a factor. Monascus cells immobilized in hydrogel were studied and exhibited decreased pigment production as a result of immobilization. This result is thought to be due to diffusional resistance of the pigment through the hydrogel beads. Addition of the adsorbent resin to the immobilized Monascus culture increased both the maximum pigment yield and the production rate above those of the free-cell fermentations. The provision of a support for the mycelium may explain enhanced pigment production by the solid-state culture. These results indicate that product diffusion from immobilized cell systems can be the limiting factor and that in situ extraction is one possible way to circumvent this problem.

Journal Article↗
PubMed2003

Pigmented ependymoma with lipofuscin and neuromelanin production.

We report an unusual case of ependymoma with pigmentation, a phenomenon that has only been described in a few cases, to our knowledge. This tumor occurred in the fourth ventricle of a 45-year-old man. It showed the typical histologic appearance of ependymoma with perivascular pseudorosettes and rare ependymal rosettes. Some tumor cells contained brown cytoplasmic pigment, which was shown histochemically to represent a mixture of lipofuscin and neuromelanin. The pigment was positive for acid-fast and periodic acid-Schiff stains and was also focally positive for Masson-Fontana and Schmorl stains (bleached by pretreatment with potassium permanganate). In addition, some other tumor cells showed a signet ring morphology as a result of prominent intracytoplasmic vacuolation. Immunohistochemically, all the tumor cells expressed glial fibrillary acidic protein, and rare pigmented tumor cells also expressed HMB-45. Ultrastructural examination showed irregularly shaped heterogeneous electron-dense bodies corresponding to the pigment, and the cytoplasmic vacuoles were formed by dilatation of intracytoplasmic lumens lined by microvilli. Since lipofuscin production can occur in normal ependymal cells and neuromelanin has been suggested to be a melanized form of lipofuscin, it is not surprising that these 2 pigments can be found in ependymoma. In all the previously reported cases, the pigment was shown to represent melanin only. In our case, the HMB-45 positivity in rare tumor cells indicated that there might also be a minor melanin component in the pigment in addition to lipofuscin and neuromelanin.

Cerebellar Neoplasms↗
PubMedDate not supplied

[Effect of cyclic compounds on pigment formation in Aspergillus niger cultures].

The mycelial pigment os Asp. niger VP has been fractionated into four fractions ehose solubility is similar to melanin pigments obtained from other sources. The addition of pyrocatechol, L-aspartic, benzoic, kojic and salicylic acids to the liquid Capek medium stimulates the fungal growth but diminishes the yield of fractions of the melanin pigment from the mycelium. Cinnamic acid does not influence the growth but also decreases the yield of the pigment. DL-tyrosine stimulates the fungal growth and produces no influence on the total yield of fractions 2, 3 and 4 from the mycelial pigment. All the cyclic compounds enhance the pigmentation of the culture liquid and give rise to the formation of fractions 2 and 3 of the melanin pigment. This latter constitutes a substantial portion of the dry matter of the fungal cell. The pigment content in the mycelium is much higher than that in the culture liquid of the corresponding culture.

Aspartic Acid↗
PubMed1991

Biochemical composition and organization of higher plant photosystem II light-harvesting pigment-proteins.

The light-harvesting complex (LHC) of barley photosystem II (PS II) was fractionated by Deriphat-polyacrylamide gel electrophoresis into five different pigmented components: one subcomplex (LHC IIb) and four pigment-proteins (LHC IIa, -c, -d, and -e). No loss of chorophyll from the components occurred during fractionation, and violaxanthin is the only photosynthetic pigment that apparently occurs in thylakoids free of association with protein. Each LHC II component has a distinct stoichiometry of neoxanthin, violaxanthin, lutein, chlorophyll a, and chlorophyll b. LHC IIa, -d, and -e were obtained as monomeric pigment-proteins, each of which contained one apoprotein Mr 31,000, 21,000, and 13,000, respectively. LHC IIc was also isolated as a monomer but it contained two poly-peptides of Mr 29,000 and 26,500, whereas the trimeric LHC IIb subcomplex (Mr 72,000) contained three subunits of Mr 28,000, 27,000, and 25,000, but not in equal stoichiometry. How the LHC II subunits are organized in PS II was examined. We isolated PS II subcomplexes which contained four of the LHC II subunits and the core complex (CC II) in unit stoichiometry; the relative strengths of association of the LHC II subunits with CC II are: LHC IIa greater than LHC IIc greater than LHC IIb greater than LHC IId. The LHC II subunits were associated with the native dimeric and not with the derived monomeric form of CC II. In addition, a multimeric LHC II sub-complex composed of the LHC IIa, LHC IIb, and LHC IId pigment-proteins was isolated. We propose that this LHC II subcomplex, which contained the Mr 28,000 and 25,000 subunits but lacked the Mr 27,000 subunit of LHC IIb and CC II. An LHC IIb pigmented fraction of LHC IIb and CC II. An LHC IIb pigmented fraction of Mr 250,000 was isolated which contained only the Mr 28,000 and 27,000 subunits. The LHC IIb subunits in this complex were the most highly phosphorylated on a protein basis. These data together with analyses of the chlorophyll b-less barley chlorina f2 mutant were used to construct a model for the LHC II pigment-protein arrangement in higher plant PS II.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1994

Ophthalmic features of minimal pigment oculocutaneous albinism.

PURPOSE: The purpose of this study is to describe the heterogeneous phenotype of individuals with an unusual type of albinism--minimal pigment oculocutaneous albinism. METHODS: Nine patients with minimal pigment oculocutaneous albinism were identified and followed for up to 11 years. The criteria were the presence of oculocutaneous albinism in association with low hairbulb tyrosinase activity in the patient and disparate activity in the parents with one parent having normal activity and the other having low tyrosinase activity. Changes in skin, hair, and ocular pigment were followed as the patients matured. As a measure of ocular pigment, iris transillumination and macular transparency were graded according to a previously published scheme. RESULTS: Patients were born with white scalp hair and skin, and nystagmus developed. Visual acuity was reduced to 20/50 to 20/200 for the group, but in one patient vision improved with maturity. Irides were blue. In seven patients, iris pigment developed, which was detected by transillumination with slit-lamp biomicroscopy, including the one patient with improved visual acuity. All patients had foveal hypoplasia, and melanin pigment in the fundi could not be detected by clinical examination. Visual acuity in the group did not correlate directly with the presence or development of iris transillumination or macular transparency. The pedigrees were consistent with an autosomal recessive inheritance pattern. CONCLUSION: This unique type of oculocutaneous albinism has heterogeneous clinical features. Minimal pigment oculocutaneous albinism appears to represent a new type of tyrosinase-related oculocutaneous albinism (OCA1MP).

Adolescent↗
PubMed2001

Skin pigmentation enhancers.

The highest incidences of cancer are found in the skin, but endogenous pigmentation is associated with markedly reduced risk. Agents that enhance skin pigmentation have the potential to reduce both photodamage and skin cancer incidence. The purpose of this review is to evaluate agents that have the potential to increase skin pigmentation. These include topically applied substances that simulate natural pigmentation: dihydroxyacetone and melanins; and substances that stimulate the natural pigmentation process: psoralens with UVA (PUVA), dimethylsulfoxide (DMSO), L-tyrosine, L-Dopa, lysosomotropic agents, diacylglycerols, thymidine dinucleotides, DNA fragments, melanocyte stimulating hormone (MSH) analogs, 3-isobutyl-1-methylxanthine (IBMX), nitric oxide donors, and bicyclic monoterpene (BMT) diols. These agents are compared with regards to efficacy when administered to melanoma cells, normal human epidermal melanocytes, animal skin, and human skin. In addition, mechanisms of action are reviewed since these may reveal issues related to both efficacy and safety. Both dihydroxyacetone and topically applied melanins are presently available to the consumer, and both of these have been shown to provide some photoprotection. Of the pigmentation stimulators, only PUVA and MSH analogs have been tested extensively on humans, but there are concerns about the safety and side effects of both. At least some of the remaining pigmentation stimulators under development have the potential to safely induce a photoprotective tan.

Animals↗
PubMed1997

Pigmented skin lesions in tyrosinase-positive oculocutaneous albinos: a study in black South Africans.

BACKGROUND: The aim of this study was to document the nature, prevalence, and distribution of pigmented skin lesions in tyrosinase-positive oculocutaneous albinism (ty-pos OCA), the most common recessive disorder in South Africa (overall prevalence, 1 in 3900). METHODS: Sixty-one black subjects with ty-pos OCA (mean age, 23 years) and 65 normally pigmented black control subjects (mean age, 29 years) were studied. RESULTS: Pigmented skin lesions not directly related to sun exposure included nevi and pigmented macules on the palms and soles. Melanocytic nevi, mostly on the trunk, were present in 82% of subjects with ty-pos OCA and in 71% of controls. The mean numbers were, however, greater in the ty-pos OCA subjects than in the controls (12 and 7, respectively), being closer to those reported in whites. Palmoplantar pigmentation was present in 75% of the control subjects, but in none of those with ty-pos OCA. The most striking sun-related lesions were dendritic freckles, which were present in 43% of ty-pos OCA subjects, and were characterized by an irregular branched shape, light to dark brown color, and large size (0.5-3.0 cm). Clinically, they resembled solar lentigines, but histologically the rete ridges were often flattened and there was no increase in the number of melanocytes. Solar keratoses occurred less frequently in ty-pos OCA subjects with dendritic freckles (50% vs. 73%), which confirmed the sun-protective role of the increased ability to form pigment. CONCLUSIONS: There were two major conclusions. Firstly pigmented nevi occur much more commonly in ty-pos OCA subjects than was previously thought, being similar in number to those found in white subjects. Secondly, dendritic freckles appear to represent a unique clinical and histologic entity found only on sun-exposed areas in ty-pos OCA subjects.

Adolescent↗
PubMed1993

Skin pigmentation due to minocycline treatment of facial dermatoses.

Fifty-four patients taking minocycline for acne or rosacea were assessed for adverse effects. Their mean duration of treatment was 17 months, and their average cumulative dose was 47 g. No symptoms attributable to the therapy were reported. Biochemistry and haematology profiles were normal. There was no evidence of an adverse effect on thyroid function. Skin pigmentation was detected in eight patients (14.8%). Five patients had diffuse facial pigmentation, and three patients had localized pigmentation at the site of a scar or injury. Diffuse pigmentation occurred only in patients who had been on treatment for 3 years or more; 50% of such patients were affected. Age and solar damage may also have been factors in this type of pigmentation. Localized pigmentation occurred at sites of previous tissue damage, and was not directly related to the duration of therapy. Patients who receive long-term minocycline therapy should be regularly monitored for the development of pigmentation.

Acne Vulgaris↗
PubMed2004

Functional genomics tools for the analysis of zebrafish pigment.

Genetic model organisms are increasingly valuable in the post-genomics era to provide a basis for comparative analysis of the human genome. For higher order processes of vertebrate pigment cell biology and development, the mouse has historically been the model of choice. A complementary organism, the zebrafish (Danio rerio), shares many of the signaling and biological processes of vertebrates, e.g. neural crest development. The zebrafish has a number of characteristics that make it an especially valuable model for the study of pigment cell biology and disease. Large-scale genetic screens have identified a collection of pigmentation mutants that have already made valuable contributions to pigment research. An increasing repertoire of genomic resources such as an expressed sequence tag-based Gene Index (The Institute for Genomic Research) and improving methods of mutagenesis, transgenesis, and gene targeting make zebrafish a particularly attractive model. Morpholino phosphorodiamidate oligonucleotide (MO) 'knockdown' of pigment gene expression provides a non-conventional antisense tool for the analysis of genes involved in pigment cell biology and disease. In addition, an ongoing, reverse-genetic, MO-based screen for the rapid identification of gene function promises to be a valuable complement to other high-throughput microarray and proteomic approaches for understanding pigment cell biology. Novel reagents for zebrafish transgenesis, such as the Sleeping Beauty transposon system, continue to improve the capacity for genetic analysis in this system and ensure that the zebrafish will be a valuable genetic model for understanding a variety of biological processes and human diseases for years to come.

Animals↗
PubMed2004

Ultraviolet radiation induces dose-dependent pigment dispersion in crustacean chromatophores.

Pigment dispersion in chromatophores as a response to UV radiation was investigated in two species of crustaceans, the crab Chasmagnathus granulata and the shrimp Palaemonetes argentinus. Eyestalkless crabs and shrimps maintained on either a black or a white background were irradiated with different UV bands. In eyestalkless crabs the significant minimal effective dose inducing pigment dispersion was 0.42 J/cm(2) for UVA and 2.15 J/cm(2) for UVB. Maximal response was achieved with 10.0 J/cm(2) UVA and 8.6 J/cm(2) UVB. UVA was more effective than UVB in inducing pigment dispersion. Soon after UV exposure, melanophores once again reached the initial stage of pigment aggregation after 45 min. Aggregated erythrophores of shrimps adapted to a white background showed significant pigment dispersion with 2.5 J/cm(2) UVA and 0.29 J/cm(2) UVC. Dispersed erythrophores of shrimps adapted to a black background did not show any significant response to UVA, UVB or UVC radiation. UVB did not induce any significant pigment dispersion in shrimps adapted to either a white or a black background. As opposed to the tanning response, which only protects against future UV exposure, the pigment dispersion response could be an important agent protecting against the harmful effects of UV radiation exposure.

Animals↗
PubMed2006

Uptake of 3H-cAMP by retinal pigment epithelium isolated from bluegill sunfish (Lepomis macrochirus).

BACKGROUND: In bluegill sunfish, the melanin-containing pigment granules of the retinal pigment epithelium undergo cyclic movements in response both to ambient lighting and circadian cues. Pigment granules aggregate into the cell body at night (in the dark), and disperse into apical processes during the day (in the light). Regulation of pigment granule aggregation in a number of fishes depends on modulating the intracellular levels of cyclic adenosine monophosphate. RESULTS: Here we show isolated RPE takes up cyclic adenosine monophosphate (cAMP) in a saturable manner, exogenously applied cAMP induces pigment granule aggregation in retinal pigment epithelium isolated from bluegill, and aggregation induced in this manner is inhibited by treatment with probenecid, an organic anion transport inhibitor. CONCLUSION: Our results raise the possibility that cAMP functions as a messenger secreted from the neural retina to signal darkness to the RPE, which takes it up. It further suggests that organic anion transport systems are the route by which cAMP crosses RPE cell membranes since probenecid inhibits extracellular cAMP from causing pigment granule aggregation.

Animals↗
PubMed2006

Genetics of pigment cells: lessons from the tyrosinase gene family.

In mammals, the melanin pigment is produced in two cell types of distinct developmental origins. The melanocytes of the skin originate form the neural crest whereas the retinal pigment epithelium (RPE) of the eye originates from the optic cup. The genetic programs governing these two cell types are thus quite different but have evolved to allow the expression of pigment cell-specific genes such as the three members of the tyrosinase-related family. Tyrosinase, Tyrp1 and Dct promoters contain a motif termed E-box which is bound by the transcription factor Mitf. These E-boxes are also found in the promoters of the corresponding fish genes, thus highlighting the pivotal role of Mitf in pigment cell-specific gene regulation. Mitf, which displays cell type-specific isoforms, transactivates the promoters of the tyrosinase gene family in both pigment cell lineages. However, specific DNA motifs have been found in these promoters, and they correspond to binding sites for RPE-specific factors such as Otx2 or for melanocyte-specific factors such as Sox10 or Pax3. The regulation of pigment cell-specific expression is also controlled by genetic elements located outside of the promoter, such as the tyrosinase distal regulatory element located at -15 kb which acts as a melanocyte-specific enhancer but also protects from spreading of condensed chromatin. Thus, by using the tyrosinase gene family as a model, it is possible to define the transcription factor networks that govern pigment production in either melanocytes or RPE.

Animals↗