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PubMed1994

Analysis of malaria pigment from Plasmodium falciparum.

The biochemical pathway for the production of malaria pigment (haemozoin) forms a fundamental difference between host and parasite and is likely to be an important drug target. A simple method for the isolation of malaria pigment is described. The resultant product retained the in vivo crystalline appearance of pigment as judged by polarizing microscopy. Conditions were found for the disaggregation and separation of pigment. As malaria pigment can adsorb drugs, haem, and iron, such separation techniques are useful tools for studies on the impairment of haemoglobin digestion and pigment formation by antimalarials.

Animals↗
PubMed2004

Severe pigment epithelial alterations in the treatment area following photodynamic therapy for classic choroidal neovascularization in young females.

PURPOSE: Although photodynamic therapy (PDT) is an established treatment for choroidal neovascularization (CNV), the mechanisms are still not completely elucidated. Damage to the retinal pigment epithelium (RPE) was observed following uncomplicated PDT in young patients. DESIGN: Observational case series. METHODS: Four female patients between the age of 26 and 39 years presented with visual loss because of classic CNV. In two 39 years old females the CNV originated secondary to a small chorioretinal scar, in a 26 and a 36-year-old woman the CNV was of idiopathic cause. All patients received standard PDT according to the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study protocol. RESULTS: One to three months after an uncomplicated PDT with verteporfin, severe pigment epithelial alterations in the treatment area were observed. The neovascular membranes responded favorably to the treatment and demonstrated fibrosis and resolution of leakage. Ophthalmoscopically and angiographically, atrophy of the retinal pigment epithelium was seen precisely delineating the size of the treatment spot used. Vision declined in two patients from 0.3 to 0.1 and 0.15 to 0.1. The two other patients demonstrated an increase of visual acuity from 0.7 to 0.9 and from 0.4 to 0.9. The retinal pigment epithelium alterations did not resolve during follow-up, but remained unchanged in area and intensity. CONCLUSIONS: Characteristic retinal pigment epithelium alterations were observed in young female patients with small classic CNV following PDT. Unusual retinal pigment epithelium damage in young female patients without any associated disease might be related to a possible inherent defect in the RPE or to the hormonal status of this specific patient population.

Adult↗
PubMed2006

Retinal pigment epithelium tears following verteporfin therapy combined with intravitreal triamcinolone.

PURPOSE: To detect patients with neovascular age-related macular degeneration (AMD) who experience retinal pigment epithelium tears after initial verteporfin therapy combined with intravitreal triamcinolone during early follow-up. DESIGN: Prospective interventional case series. METHODS: Forty-five consecutive patients with choroidal neovascularization (CNV) in AMD were treated with verteporfin therapy combined with 4 mg of intravitreal triamcinolone. Optical coherence tomography (OCT), visual acuity, and fluorescein angiography were performed. RESULTS: Two eyes with a predominantly classic CNV developed a retinal pigment epithelium tear. An early onset tear could be differentiated from a delayed onset tear. OCT showed an increased depth signal in areas of missing retinal pigment epithelium and a wavy, contracted, and elevated retinal pigment epithelium band. CONCLUSIONS: Retinal pigment epithelium tears can occur despite adding intravitreal triamcinolone to verteporfin therapy. OCT shows characteristic changes in the evolution of retinal pigment epithelium tears after combination therapy.

Choroidal Neovascularization↗
PubMed2006

Retinal pigment epithelial tear following intravitreal pegaptanib sodium.

PURPOSE: To report two cases of a retinal pigment epithelial tear after intravitreal injection of pegaptanib sodium. To our knowledge, this is the first report of this finding after intraocular antivascular endothelial growth factor therapy. DESIGN: Observational case reports. METHODS: Two patients presented with occult choroidal neovascularization and associated serous pigment epithelial detachment that was a result of age-related macular degeneration. Both patients were treated with an intravitreal injection of pegaptanib sodium. RESULTS: One patient developed a retinal pigment epithelium tear one week after the intravitreal injection. The second patient developed a retinal pigment epithelium tear eight weeks after treatment. CONCLUSIONS: Although these cases may represent natural history, there should be a high index of suspicion for retinal pigment epithelium tears in patients who report significant visual deterioration after intravitreal injection of pegaptanib sodium. Further studies are needed to determine whether angiographic subtypes of choroidal neovascular membranes are more susceptible to developing retinal pigment epithelium tears after treatment with antivascular endothelial growth factor agents.

Aged↗
PubMed2006

Trafficking of osteonectin by retinal pigment epithelial cells: evidence for basolateral secretion.

Osteonectin is a glycoprotein that modulates several aspects of cellular behaviour including proliferation and adhesion. The retinal pigment epithelium forms a continuous monolayer of polarised cells immediately bellow the neuroretina, and is integral to the homeostasis of photoreceptor cells. While osteonectin is expressed by normal retinal pigment epithelium in situ, its expression is significantly increased in retinal pigment epithelial cells associated with several common retinal diseases. This pattern of expression implies an important role for osteonectin in the biology of retinal pigment epithelial cells. However, the trafficking, processing, and eventual fate of osteonectin in these cells is not clear at present. Although the theoretical report of a leader sequence within the osteonectin open reading frame and its extracellular presence in some tissues indirectly support secretion of the protein, there is no direct experimental demonstration of the secretion route to date. As a first step towards understanding the role of osteonectin in retinal pigment epithelium, we studied the intracellular distribution and trafficking of the protein in living cells. Here, we present experimental evidence that a precursor osteonectin fusion protein is targeted to the endoplasmic reticulum/Golgi pathway, with a likely basal secretion in retinal pigment epithelial cells. In addition, we show that the precursor osteonectin protein having the leader sequence masked fails to undergo secretion leading to cell death, a phenotype which may be of relevance not only for retinal pathology, but also for other diseases such as the bone disorder known as pseudoachondroplasia that is associated with a lack of osteonectin secretion.

Achondroplasia↗
PubMed2005

Mechanisms for the induction of HNE- MDA- and AGE-adducts, RAGE and VEGF in retinal pigment epithelial cells.

Pathological features of age-related macular degeneration such as the formation of extracellular deposits and neovascularization are frequently viewed as outcomes of compromising processes within retinal pigment epithelial cells, but the initiating circumstances are poorly understood. Here we tested the hypothesis that photooxidation events initiated by A2E, a blue light-excitable aging fluorophore of the retinal pigment epithelium, can set the stage for altered cellular signaling and changes in the expression of genes that can impact the extracellular milieu. Proteins modified by lipid peroxidation products (4-hydroxynonenal; malondialdhyde) and advanced glycation end products were detected at sites of blue light irradiation both in association with the cultured A2E-laden retinal pigment epithelial cells and within the fibronectin substrate on which the cells were grown. RAGE, the cell surface receptor that transduces the effects of advanced glycation end products, was also upregulated, and RAGE expression co-localized with the deposition of advanced glycation end products. Blue light triggered alterations in gene expression was also evidenced by elevations in both transcripts and protein for vascular endothelial growth factor, a potent angiogenic and permeability-enhancing factor. These findings indicate that cell associated and extracellular modification of proteins by lipid peroxidation products and advanced glycation end products together with increased expression of RAGE and vascular endothelial growth factor may be induced consequent to blue light illumination of A2E-burdened retinal pigment epithelial cells. Thus, photooxidative events that are not an immediate threat to retinal pigment epithelial cell viability may nevertheless elicit sustained perturbation that could ultimately alter neighboring tissues and impact retinal pigment epithelial cell function.

Aldehydes↗
PubMed2005

Role of pigmentation in protecting Bacillus sp. endospores against environmental UV radiation.

Bacillus endospores show different kinds of pigmentation. Red-pigmented spores of Bacillus atrophaeus DSM 675, dark-gray spores of B. atrophaeus(T) DSM 7264 and light-gray spores of B. subtilis DSM 5611 were used to study the protective role of the pigments in their resistance to defined ranges of environmental UV radiation. Spores of B. atrophaeus DSM 675 possessing a dark-red pigment were 10 times more resistant to UV-A radiation than those of the other two investigated strains, whereas the responses to the more energetic UV-B and UV-C radiation were identical in all three strains. The methanol fraction of the extracted pigment from the spores absorbs in the associated wavelength area. These results indicate that the carotene-like pigment of spores of B. atrophaeus DSM 675 affects the resistance of spores to environmental UV-A radiation.

Bacillus↗
PubMed2005

Comparative analysis of Cryptococcus neoformans acid-resistant particles generated from pigmented cells grown in different laccase substrates.

Cryptococcus neoformans produces pigments in vitro in the presence of exogenous substrate. We characterized acid-resistant particles isolated from pigmented cells grown in L-dopa, methyl-dopa, (-)-epinephrine or (-)-norepinephrine. The goals of this study were to determine whether pigments made from each of these substrates were melanins and the consequences of pigmentation on related cell characteristics. The greatest yield of acid-resistant particles occurred with methyl-dopa followed by L-dopa. Electron microscopy indicated that L-dopa and methyl-dopa produced particles with thicker shells. The mAb 6D2 reacted with all particles, but a lower reactivity was observed with epinephrine-derived particles. ESR analysis revealed that epinephrine-derived particles failed to produce a stable free radical signal typical of melanins. Growth of C. neoformans in different substrates affected cell and capsule size but not capsule induction. Hence, the type of pigment produced by C. neoformans is dependent on the substrate and not all pigments meet the criteria for melanins.

Chromatography, High Pressure Liquid↗
PubMed2003

Cloning and functional analysis of ascidian Mitf in vivo: insights into the origin of vertebrate pigment cells.

The microphthalmia-associated transcription factor (Mitf) is a basic-helix-loop-helix-leucine zipper (bHLH-ZIP) transcription factor essential for the development and function of all melanin-producing pigment cells in vertebrates. To elucidate the evolutionary history of Mitf and the antiquity of its association with pigment cells, we have isolated and characterized HrMitf, a sole member of the Mitf-TFE bHLH-ZIP subfamily in the ascidian Halocynthia roretzi. Maternal HrMitf mRNA is detected in the fertilized egg and in the animal hemisphere from 4-cell stage through the gastrula stage. From the neurula through the early tailbud stage, HrMitf is preferentially expressed in the pigment-lineage cells that express the lineage-specific melanogenesis genes tyrosinase (HrTyr) and Tyrp. Overexpression of HrMitf induced ectopic expression of HrTyr enzyme activity in mesenchymal cells where the same enzyme activity was induced by overexpression of HrPax3/7, suggesting that a part(s) of the Pax3-Mitf-tyrosinase gene regulatory cascade seen in vertebrate melanocytes is operative during ascidian embryogenesis. We also show HrMitf and mouse Mitf-A, a Mitf isoform abundantly expressed in pigmented epithelial cells, share similar functional characteristics. These results suggest antiquity of the association of the Mitf-TFE subfamily with pigment cells and may support the idea that acquisition of multiple promoters (isoforms) by an ancestral Mitf gene has allowed the evolution of multiple pigment cell types.

Amino Acid Sequence↗
PubMed2004

Mutagenesis and reconstitution of middle-to-long-wave-sensitive visual pigments of New World monkeys for testing the tuning effect of residues at sites 229 and 233.

The colour vision polymorphism of New World monkeys results from allelic variations of the middle-to-long-wave-sensitive (M/LWS) visual pigments. On the basis of sequence comparison, spectral differences among the alleles have been ascribed to amino acid residues at sites 180, 229, 233, 277, and 285. While the significant spectral effects have been demonstrated for sites 180, 277, and 285 by site-directed mutagenesis for a large number of vertebrate M/LWS pigments (the "three-site rule"), effects at sites 229 and 233 remain untested. Here we measured absorption spectra of the reconstituted M/LWS pigments from the tri-allelic squirrel monkey (Saimiri sciureus) and the mono-allelic owl monkey (Aotus trivirgatus). The peak absorption spectra (lambdamax) of Saimiri pigments were 532, 545, and 558 nm and that of Aotus pigment 539 nm, being consistent with the prediction from the three-site rule. Our site-directed mutagenesis for sites 229 and 233 showed that their mutational effects for lambdamax values were negligible. These results preclude the necessity of examining exon 4, encoding the residues at sites 229 and 233, of M/LWS pigment genes for colour-vision typing of New World monkeys.

Amino Acid Sequence↗
PubMed2001

Retinal pigment epithelial tear after transpupillary thermotherapy for choroidal neovascularization.

PURPOSE: To describe two patients who developed a retinal pigment epithelial tear after transpupillary thermotherapy for choroidal neovascularization. METHOD: Case reports. RESULTS: Retinal pigment epithelial (retinal pigment epithelium) tear developed in 2 (8%) of 25 eyes after transpupillary thermotherapy for occult choroidal neovascularization associated with age-related macular degeneration. In both eyes, the retinal pigment epithelium tear developed between the treatment session and first post-treatment examination. In both eyes, the visual acuity was unchanged, but the complication of retinal pigment epithelium tear may result in decreased visual acuity when transpupillary thermotherapy is performed in an eye with good initial visual acuity. CONCLUSION: Retinal pigment epithelium tear appears to occur more frequently after transpupillary thermotherapy for poorly defined choroidal neovascularization than after conventional laser photocoagulation for poorly defined choroidal neovascularization.

Aged↗
PubMed2003

Foveal congenital hypertrophy of the retinal pigment epithelium in the setting of geographic atrophy from age-related macular degeneration.

PURPOSE: To report a case of presumed congenital hypertrophy of the retinal pigment epithelium in the fovea of an 88-year-old woman in the setting of geographic atrophy from age-related macular degeneration. DESIGN: Observational case report. METHODS: An 88-year-old woman was examined. RESULTS: Best-corrected visual acuity was 20/63 in the right eye and 20/50 in the left eye. Multifocal areas of geographic atrophy and large-sized drusen were seen in the maculae of both eyes. Biomicroscopic examination of the right eye showed hyperpigmentation consistent with congenital hypertrophy of the retinal pigment epithelium through the center of the macula. No prior photographic documentation of the retina was available. CONCLUSION: This case suggests that foveal congenital hypertrophy of the retinal pigment epithelium may be seen in the setting of macular geographic atrophy. Although it is theoretically possible that the hyperpigmentation is reactive rather than congenital, the pigmentation is typical for congenital hypertrophy and is unlike any reactive pigmentation in our experience or described in a MEDLINE search of features of age-related macular degeneration. The case suggests that a hypertrophic process of the retinal pigment epithelium may coexist within or immediately adjacent to the anatomic boundaries of an atrophic process such as geographic atrophy from age-related macular degeneration.

Aged↗
PubMed2003

Increased periocular pigmentation with ocular hypotensive lipid use in African Americans.

PURPOSE: To report increased eyelid pigmentation as an adverse side effect associated with topical ocular hypotensive lipids in African Americans. DESIGN: Interventional case series. METHODS: Two African-American patients with open-angle glaucoma are described in whom increased eyelid pigmentation developed 1 month to 5 months after beginning treatment with either latanoprost or bimatoprost. RESULTS: Latanoprost was discontinued in an African-American patient, and pigmentation gradually diminished by 3 months after cessation of latanoprost. Increased eyelid pigmentation and increased eyelash length were noted in another African-American patient after just 4 weeks on bimatoprost. CONCLUSIONS: An increase in eyelid pigmentation and eyelash growth is a possible complication of topical ocular hypotensive lipid therapy, even in African-American patients. The changes seems to present earlier after bimatoprost treatment then after latanoprost treatment. Cessation of these medications may lead to loss of induced pigmentation.

Amides↗
PubMed1980

PIgment epithelial diseases with abnormal choroidal perfusion.

Sixteen patients, seen during the first week of their disease, had swelling of the retinal pigment epithelium and angiographic evidence of a widespread abnormality of choroidal filling. The patients fell into three groups: In Group 1 there were multifocal pigment epithelial lesions identical to those of acute posterior multifocal placoid pigment epitheliopathy. In Group 2 the pigment epithelial lesions were confluent. The retina was not detached in either of the these groups. In Group 3, multifocal lesions of the pigment epithelium were associated with retinal detachment. We postulated that all patients had diffuse choroidal hypoperfusion and focal pigment epithelial infarct which, in turn, may have been caused by a variety of basic disorders. We detected no relevant systemic abnormalities in any of the patients.

Adolescent↗
PubMed1994

Autosomal recessive retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium.

Retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium is a rare form of retinitis pigmentosa that starts early in life with preservation of retinal pigment epithelium adjacent to and under the retinal arterioles and that has hitherto been described as an isolated form. We examined 22 patients from one large family, together with two isolated patients, and confirmed the presumed autosomal recessive mode of inheritance in this type of retinitis pigmentosa. New findings associated with retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium were asteroid hyalosis in four (17%) of 24 patients, tortuosity of retinal arterioles in 11 (46%) of 24 patients, peripheral regions of opacified vessels in eight (33%) of 24 patients, and preservation not only of the para-arteriolar pigment epithelium, but also of the peripheral retinal pigment epithelium in 13 (54%) of 24 patients. Previously reported signs present in these patients were nystagmus in six (25%) of 24 patients, hypermetropia in 23 (96%) of 24 patients, optic nerve head drusen in nine (38%) of 24 patients, vascular sheathing in 11 (46%) of 24 patients, maculopathy in all 24 patients (100%), yellow round deposits in the posterior pole in nine (38%) of 24 patients, exudates resembling those in Coats' disease in two (8%) of 24 patients, visual field defects in all 24 patients (100%), and nondeductible electroretinograms in 21 (91%) of 23 patients. Linkage analysis carried out in the large family resulted in the assignment of a gene for retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium to chromosome 1q31-q32.1.

Adolescent↗
PubMed1996

Inflammatory properties of bile from dogs with pigment gallstones.

BACKGROUND: Gallbladder inflammation and mucus hypersecretion are prominent features of cholesterol and pigment gallstones in humans and animals. The factors leading to inflammation and mucus hypersecretion are poorly understood. These studies examine the inflammatory potential of bile from dogs with pigment gallstones. METHODS: Dogs fed a methionine-deficient diet that produces pigment gallstones by 6 weeks were compared to normal dogs. Mucus layer thickness, myeloperoxidase activity, and interleukin-1-like activities were measured in canine gallbladder. The inflammatory potential of canine bile was determined by measuring mucus layer thickness, sodium absorption, myeloperoxidase activity and interleukin-1-like activity in guinea pig gallbladders exposed to normal and lithogenic canine bile for 4 hours. RESULTS: Mean mucus layer thickness, myeloperoxidase, and interleukin-1 activity were significantly greater in canine gallbladders containing pigment gallstones. Bile from dogs with pigment gallstones markedly increased mucus layer thickness, myeloperoxidase activity, and interleukin-1 activity and decreased sodium absorption in normal guinea pig gallbladder. These effects were not eliminated by centrifuging bile to remove crystals and gallstones. CONCLUSIONS: Canine bile from dogs with pigment gallstones contains soluble factors capable of causing inflammation in the gallbladder wall.

Animals↗
PubMed1977

Synthetic pigment analogues of the purple membrane protein.

Nonphysiological analogues of retinal have been shown to form pigments in reactions with the apoprotein of the purple membrane of Halobacterium halobium. Both the all-trans and 13-cis isomers of a retinal analogue, having an elongated chain with an extra double bond, formed pigments. Unlike the native all-trans and 13-cis retinal1-based pigments, the new pigments were not interconvertible with each other and were unstable against hydroxylamine. When incorporated into phospholipid vesicles, they showed no proton pumping activity upon illumination. The ability of the extended-length retinal to form pigments contrasts with its nonreactivity with opsin (apoprotein of rhodopsin), suggesting a less stringent binding site for the purple membrane chromophore. All-trans retinal2 also combined with bleached purple membrane to form a blue pigment absorbing at ca. 590 nm. Like the native purple membrane, the blu membrane showed proton pumping activity upon illumination in phospholipid vesicles.

Apoproteins↗
PubMed1983

Photochemistry of two rhodopsinlike pigments in bacteriorhodopsin-free mutant of Halobacterium halobium.

Two photocycles due to two different pigments were found in membrane vesicles of a bacteriorhodopsin-free mutant of Halobacterium halobium. A pigment absorbing approximately 590 nm halorhodopsin (HR) underwent a faster photocycle with a phototransient at approximately 490 nm (half-time of decay, tau 1/2 = 10 ms). Another third rhodopsinlike pigment (TR) absorbing approximately 580 nm underwent a slower photocycle accompanying a phototransient absorbing below 410 nm (tau 1/2 = 0.8s). The photocycles were measured under various conditions of temperature, NaCl concentration, pH, and in the presence of cholate. All results obtained support the notion that the two photocycles are independent of each other, and the fast or the slow cycle can be abolished after these treatments. At alkaline pH, the wavelength of maximum absorbance of both pigments shifted to blue, but the magnitude of the shift of the pigment undergoing the slow photocycle was much greater than the other. The ratio of the content of the two pigments varies among bacteriorhodopsin-free mutants.

Bacteriorhodopsins↗