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PubMed1991

Dependence of intraocular straylight on pigmentation and light transmission through the ocular wall.

The straylight function of the human eye depends on eye color, especially at larger angles of scattering. As a potential cause for this dependence, transmission of light through the ocular wall was measured, using a psychophysical method. For a light-blue eye effective transmission of the iris was 1% for red and 0.2% for green light. Also the eyewall around the iris transmits a significant amount of light. For the dark-brown eyes of pigmented individuals transmission is lower by two orders of magnitude. Although important, transmission proved to be only partly responsible for the pigmentation dependence, the other cause probably being reflection from the fundus.

Adult↗

PubMed1997

Visible and ultraviolet-B ocular-ambient exposure ratios for a general population. Salisbury Eye Evaluation Project Team.

PURPOSE: To estimate the numerical value of the ocular-ambient exposure ratio (OAER) (ratio of the facial exposure to that on a horizontal plane) as a function of wavelength band, season, and job category and to establish the effect of various modifiers, such as geography and the use of hats, for use in general population studies. METHODS: Two hundred sixty-four persons within several job categories representing the jobs in our Salisbury, Maryland, population were instrumented with ultraviolet-B (UVB) and visible band sensors for 1 complete day. Studies were done over all four seasons, both with and without hats. RESULTS: OAERs in the UVB wavelength band generally are higher than in the visible (13% versus 6%), display no significant variation with job category, show a seasonal effect (highest in the winter-spring [18%], lowest in the summer [10%], and intermediate in the fall [14%]), and are reduced 34% by the use of hats. In the visible wavelength band, OAERs are affected weakly by job function, although this variation is not significant, display a seasonal effect with three seasons as in the UVB, and are not affected significantly by the use of hats. In neither the UVB nor the visible portions of the spectrum did the authors find an effect on the OAER due to photophobia or eye color. CONCLUSIONS: With the authors' exposure model, the authors have at their disposal a valuable tool for exploring the relation between UVB, UVA, and visible radiation and a number of age-related eye diseases.

Environmental Exposure↗

PubMed1984

Assortative marriage for physical characteristics in newlyweds.

The objective of this study was to estimate the degree of spouse resemblance in the first 6 months of marriage and to compare these estimates with those of previous studies on long-standing marriages. The participants, 215 couples, were selected from the marriage licenses issued in two counties within the San Francisco Bay Area. They attended one of several group sessions in which questionnaires were filled out and forearm length measurements were taken. Only the results for the couples of European ancestry (N = 164) are presented here since the other subsamples were too small to analyze separately. The husband-wife correlations for body size were found to be essentially equal to those in long-standing marriages. Thus, it appears that physical resemblance in couples is the result of initial assortment rather than convergence arising from long cohabitation. A significant residual husband-wife correlation for weight was found after statistically partialing out height. It may be that assortative marriage for food habits and attractiveness produces spouse resemblance in weight, independently of height. Alternatively, convergence in eating habits may occur during courtship and the early months of marriage which may increase the resemblance in weight. There was very little homogamy for eye color independently of race, and no evidence of assortative marriage for handedness.

Adolescent↗

PubMed1984

Purification and properties of the enzymes from Drosophila melanogaster that catalyze the conversion of dihydroneopterin triphosphate to the pyrimidodiazepine precursor of the drosopterins.

The enzyme system responsible for the conversion of 2-amino-4-oxo-6-(D-erythro-1',2',3'-trihydroxypropyl)-7,8-dihyd roptridine triphosphate (dihydroneopterin triphosphate or H2-NTP) to 2-amino-4-oxo-6-acetyl-7,8-dihydro-3H,9H-pyrimido[4,5-b]-[1,4]diazepine (pyrimidodiazepine or PDA), a precursor to the red eye pigments, he drosopterins, has been purified from the heads of Drosophila melanogaster. The PDA-synthesizing system consists of two components, a heat-stable enzyme and a heat-labile enzyme. The heat-stable enzyme can be replaced by sepiapterin synthase A, a previously purified enzyme required for the Mg2+-dependent conversion of H2-NTP to an unstable compound that appears to be 6-pyruvoyltetrahydropterin (pyruvoyl-H4-pterin). The heat-labile enzyme, purified to near-homogeneity and termed PDA synthase (Mr = 48,000), catalyzes the conversion of pyruvoyl-H4-pterin to PDA in a reaction requiring the presence of reduced glutathione. Because PDA is two electrons more reduced than pyruvoyl-H4-pterin, the reducing power required for this transformation is probably supplied by glutathione. The PDA-synthesizing system requires the presence of another thiol-containing compound such as 2-mercaptoethanol when incubation conditions 2-mercaptoethanol is no longer required. Evidence is presented to indicate that the Drosophila eye color mutant, sepia, is missing PDA synthase.

Alcohol Oxidoreductases↗

PubMed1981

Do blue-eyed white cats have normal or abnormal retinofugal pathways?

Three white cats that had blue eyes and no tapetum were studied by behavioral, electrophysiological, and anatomical methods in order to determine whether they showed evidence of abnormal retinofugal pathways comparable to those found in Siamese cats and in other mammalian forms having melanin deficits. The three cats were normal in every respect. However, several other white cats, obtained subsequently, do show an abnormality of the retinogeniculate pathway identical to the abnormality of Siamese cats. Cats of the second type are thought to be homozygous for the Siamese gene and also the express the White gene. Because the characteristics Siamese pigmented "points" fail to develop in the presence of the white gene, cats of the second type are not distinguishable from other white cats on the basis of eye color or coat color. In terms of their central visual pathways and of their patterns, however, they are recognizably Siamese. It is not known how common "crypto-Siamese" cats are in the white cat population, but the possibility of their occurrence suggests that, in general, white cats should not be used for studied of the central visual pathways.

Animals↗

PubMed2006

The association between host susceptibility factors and uveal melanoma: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis, using observational studies, to examine the association between host susceptibility factors and uveal melanoma. METHODS: A review of 132 published reports on risk factors for uveal melanoma revealed 10 case-control studies that provided enough information to calculate odds ratios (ORs) and standard errors for host susceptibility factors. Data from these studies were extracted and categorized. Summary statistics were calculated for all risk factors reported by at least 4 independent studies. RESULTS: Summary statistics using meta-analysis are presented as ORs and their 95% confidence intervals (CIs). Statistically significant risk factors include light eye color (OR, 1.75 [95% CI, 1.31-2.34]), using 10 studies (1732 cases); fair skin color (OR, 1.80 [95% CI, 1.31-2.47]), using 5 studies (586 cases); and ability to tan (OR, 1.64 [95% CI, 1.29-2.09]), using 6 studies (1021 cases). Blond or red hair color, using 7 studies (1012 cases), was not a statistically significant independent risk factor (OR, 1.02 [95% CI, 0.82-1.26]). CONCLUSION: This meta-analysis yielded strong evidence associating the host susceptibility factors of iris color, skin color, and ability to tan with uveal melanoma.

Case-Control Studies↗

PubMed2000

Genetic and biochemical analysis of brown eye mutation in Drosophila nasuta nasuta and Drosophila nasuta albomicans.

By analyzing the progeny of crosses involving brown eye mutants and the wild types in two members of Drosophila nasuta subgroup namely D. n. nasuta and D. n. albomicans we could show that the mutant gene is recessive, located in the chromosome 2 and the alleles of this gene are present at different loci. A study of fitness in the eye color mutants in comparison with the wild types revealed that D. n. nasuta mutant has higher viability at both 25+/-1 degrees C and ambient temperatures; while D. n. albomicans mutant has faster rate of development only at 25+/-1 degrees C. Quantitative analysis of eye pigments in the mutants revealed that there is biosynthesis of both pteridines and xanthommatins unlike in bw/bw of D. melanogaster, where only xanthommatins are synthesized. In both the species, the pteridine quantities in mutants are similar; whereas xanthommatin quantity in bw(n)/bw(n) is 10 times higher than that of bw(a)/bw(a). Further, the F1 progeny of intraspecific crosses (wild type X mutant) are found to have high amounts of pteridine, even when compared with parental wild type.

Animals↗

PubMed1991

Breast cancer and cerebral laterality.

In reviewing and summarizing work at our institution, we have identified some surprising consistencies in patients with breast cancer. Breast cancer shows four features of cerebral laterality: excess left-handedness, atypical season-of-birth patterns, the risk factor of advanced maternal age, and an association with prenatal sex hormones. Since hypopigmentation also relates to cerebral laterality, a consequence of the association of breast cancer and cerebral laterality is that eye color should be measured as a function of side of disease and age at diagnosis in women with breast cancer.

Breast Neoplasms↗

PubMed2001

Characterization of melanocortin-1 receptor gene variants in uveal melanoma patients.

PURPOSE: Allelic variations of the melanocortin-1 receptor (MC1R) gene have been linked to red hair and sun-sensitive skin types and may play a role in the susceptibility to develop cutaneous malignant melanoma (CMM). To define the role of MC1R gene in uveal melanoma, a case control study was performed, in which the presence of MC1R gene variations in uveal melanoma patients was compared with that of healthy controls. METHODS: MC1R gene variants were analyzed in 162 uveal melanoma patients and 255 healthy controls. After genomic DNA was isolated from venous blood, the MC1R gene was amplified by polymerase chain reaction (PCR) and examined for the presence of variants by single-strand conformation polymorphism (SSCP) analysis. Participants were asked to complete a questionnaire regarding skin type, eye color, and hair color. RESULTS: No disparity was found between the distribution of the MC1R gene variants in both groups. Furthermore, no associations between MC1R genotype and pigment phenotype were found. In contrast to CMM, uveal melanoma patients did not show specific MC1R gene variants. Compared with controls, most uveal melanoma patients had blue eyes (65%, P = 0.060) and skin type III (56%); however, in the uveal melanoma group the presence of dark blond hair was significantly elevated (46%, P = 0.030). These findings are in contrast with studies on CMM, where most patients have skin type II and red/fair hair. CONCLUSIONS: These data suggest that MC1R variants do not play a role in the susceptibility to develop uveal melanoma. Furthermore, most uveal melanoma patients share phenotypic characteristics that differ from findings in CMM patients.

Adult↗

PubMed2004

A 5-year, multicenter, open-label, safety study of adjunctive latanoprost therapy for glaucoma.

OBJECTIVE: To evaluate the 5-year safety and efficacy of adjunctive 0.005% latanoprost once daily. METHODS: Patients with primary open-angle or exfoliation glaucoma who completed a 3-year, open-label, uncontrolled, prospective trial could enter a 2-year extension phase. High-resolution color photographs of irides were taken at baseline and at 14 subsequent visits. Photographs were assessed for change in iris pigmentation compared with baseline. Intraocular pressures and adverse events were recorded. MAIN OUTCOME MEASURE: Development and progression of increased iris pigmentation over 5 years. RESULTS: Of the 519 original patients, 380 enrolled in the extension phase with approximately 89% having an eye color known to be susceptible to color change. After 5 years, most patients had no increase in iris pigmentation, but certain colored irides exhibited notably greater susceptibility than others. For those whose irides did change, onset occurred during the first 8 months in 74% and during the first 24 months in 94%. No patient developed an increase in pigmentation after month 36; the rate of progression decreased over time. Adverse event profiles were similar for patients with and without increased pigmentation. The overall mean intraocular pressure reduction from baseline of 25% was sustained with no need for change in intraocular pressure-lowering treatment in 70% of the eyes. CONCLUSION: Latanoprost therapy is safe and well tolerated for long-term treatment of open-angle glaucoma.

Adult↗

PubMed1999

Dermatologic manifestations of Hermansky-Pudlak syndrome in patients with and without a 16-base pair duplication in the HPS1 gene.

BACKGROUND: Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism, a platelet storage pool deficiency, and lysosomal accumulation of ceroid lipofuscin. Patients with HPS from northwest Puerto Rico are homozygous for a 16-base pair (bp) duplication in exon 15 of HPS1, a gene on chromosome 10q23 known to cause the disorder. OBJECTIVE: To determine the dermatologic findings of patients with HPS. DESIGN: Survey of inpatients with HPS by physical examination. SETTING: National Institutes of Health Clinical Center, Bethesda, Md (a tertiary referral hospital). PATIENTS: Sixty-five patients aged 3 to 54 years were diagnosed on the basis of the absence of platelet dense bodies in individuals with albinism and a bleeding diathesis. The presence of a 16-bp duplication in HPS1 was determined by polymerase chain reaction amplification; 40 patients were homozygous for the duplication and 25 lacked the duplication. All patients with the duplication were from northwest Puerto Rico; all patients without the duplication were non-Puerto Rican except 4 from central Puerto Rico. RESULTS: Both patients homozygous for the 16-bp duplication and patients without the duplication displayed skin color ranging from white to light brown. Patients with the duplication, as well as those lacking the duplication, had hair color ranging from white to brown and eye color ranging from blue to brown. New findings in both groups of patients with HPS were melanocytic nevi with dysplastic features, acanthosis nigricans-like lesions in the axilla and neck, and trichomegaly. Eighty percent of patients with the duplication exhibited features of solar damage, including multiple freckles, stellate lentigines, actinic keratoses, and, occasionally, basal cell or squamous cell carcinomas. Only 8% of patients lacking the 16-bp duplication displayed these findings. As a group, the patients with the duplication lived closer to the equator than those without the duplication. CONCLUSION: Patients with HPS exhibit wide variation in pigmentation and dermatologic findings.

Adolescent↗

PubMed1974

Fast electrical potential from a long-lived, long-wavelength photoproduct of fly visual pigment.

A rapid electrical potential, which we have named the M-potential, can be obtained from the Drosophila eye using a high energy flash stimulus. The potential can be elicited from the normal fly, but it is especially prominent in the mutant norp A(P12) (a phototransduction mutant), particularly if the eye color pigments are genetically removed from the eye. Several lines of evidence suggest that the M-potential arises from photoexcitation of long-lived metarhodopsin. Photoexcitation of rhodopsin does not produce a comparable potential. The spectral sensitivity of the M-potential peaks at about 575 nm. The M-potential pigment (metarhodopsin) can be shown to photoconvert back and forth with a "silent pigment(s)" absorbing maximally at about 485 nm. The silent pigment presumably is rhodopsin. These results support the recent spectrophotometric findings that dipteran metarhodopsin absorbs at much longer wavelengths than rhodopsin. The M-potential probably is related to the photoproduct component of the early receptor potential (ERP). Two major differences between the M-potential and the classical ERP are: (a) Drosophila rhodopsin does not produce a rapid photoresponse, and (b) an anesthetized or freshly sacrificed animal does not yield the M-potential. As in the case of the ERP, the M-potential appears to be a response associated with a particular state of the fly visual pigment. Therefore, it should be useful in in vivo investigations of the fly visual pigment, about which little is known.

Animals↗

PubMed2000

Lutein improves visual function in some patients with retinal degeneration: a pilot study via the Internet.

PURPOSE: The purpose of this article is to examine the effects of lutein supplementation on visual acuity, central visual-field area, and subjective visual disturbances in retinitis pigmentosa (RP) and related retinal degenerations, in an international study population recruited via an Internet mailing list. METHODS: Sixteen participants (13 with RP, three with other retinal degenerations) completed a 26-week program of lutein supplementation (40 mg/day for 9 weeks, 20 mg/day thereafter); 10 participants also took 500-mg docosahexaenoic acid (DHA)/day, vitamin B complex, and digestive enzymes. Ten participants previously taking vitamin A and/or beta-carotene continued those supplements throughout the study. Participants self-tested their visual acuity on their computer screen and their central visual-field extent on a wall chart, weekly for 14 weeks, bi-weekly thereafter. RESULTS: Mean visual acuity improved by 0.7 dB and mean visual-field area by 0.35 dB. Improvements started 2 to 4 weeks after supplementation began, and plateaued at 6 to 14 weeks. Visual acuity gains were strongly correlated with eye color: 1.2 dB in seven blue-eyed participants, but 0.3 dB in seven dark-eyed participants. Participants who received previous supplements showed greater benefits in central visual-field area (0.55 dB) than those not receiving previous supplements (no change). No significant effects of age, sex, disease stage, or study supplement were found. CONCLUSIONS: Short-term vision improvements after lutein supplementation--previously reported in age-related macular degeneration--also occur in RP, especially in blue-eyed individuals; vitamin A may increase visual field benefits.

Administration, Oral↗

PubMed1989

Homeosis and the interaction of zeste and white in Drosophila.

Transvection effects in Drosophila melanogaster suggest a form of gene modulation that is responsive to the proximity of homologous genes. These effects have been well characterized at bithorax and decapentaplegic, and in the interaction between the zeste and white genes. The mechanistic basis for transvection is not known. As part of a genetic analysis of transvection, a study is being made of a class of mutations defined as modifiers of the eye color resulting from the interaction of zeste and white. This report details the observations that several of these mutations also have homeotic effects.

Animals↗

PubMed2000

Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype?

Risk of cutaneous malignant melanoma (CMM) is increased in sun-exposed whites, particularly those with a pale complexion. This study was designed to investigate the relationship of the melanocortin-1 receptor (MC1R) genotype to CMM risk, controlled for pigmentation phenotype. We report the occurrence of five common MC1R variants in an Australian population-based sample of 460 individuals with familial and sporadic CMM and 399 control individuals-and their relationship to such other risk factors as skin, hair, and eye color; freckling; and nevus count. There was a strong relationship between MC1R variants and hair color and skin type. Moreover, MC1R variants were found in 72% of the individuals with CMM, whereas only 56% of the control individuals carried at least one variant (P<.001), a finding independent of strength of family history of melanoma. Three active alleles (Arg151Cys, Arg160Trp, and Asp294His), previously associated with red hair, doubled CMM risk for each additional allele carried (odds ratio 2.0; 95% confidence interval 1. 6-2.6). No such independent association could be demonstrated with the Val60Leu and Asp84Glu variants. Among pale-skinned individuals alone, this association between CMM and MC1R variants was absent, but it persisted among those reporting a medium or olive/dark complexion. We conclude that the effect that MC1R variant alleles have on CMM is partly mediated via determination of pigmentation phenotype and that these alleles may also negate the protection normally afforded by darker skin coloring in some members of this white population.

Data Interpretation, Statistical↗

PubMed1980

Functions of the white and topaz loci of Lucilia cuprina in the production of the eye pigment xanthommatin.

The white and topaz eye color mutants of L. cuprina are defective in the production of the brown screening pigment xanthommatin. Both white and topaz mutants were found to be unable to accumulate xanthommatin precursors in the larval malpighian tubules, correlating with their reduced early pupal level of this metabolite. In addition, white mutants showed reduced rates of accumulation of kynurenine and 3-hydroxykynurenine in the adult eyes. Another mutant strain, grape, was also defective in its ability to accumulate these xanthommatin precursors in the eyes, although accumulation was normal in the larval tubules. In contrast, the topaz mutants were found to be normal in eye accumulation, although tubule accumulation was markedly abnormal. These properties of the white and topaz mutants of L. cuprina are compared with those of the white and scarlet mutants of D. melanogaster, and it seems likely that in the two species these genes are involved with the uptake or storage of xanthommatin precursors in specific tissues.

Animals↗

PubMed1993

Fixed-distance latent class models for the analysis of sets of two-way contingency tables.

This paper develops and describes the application of modified latent class models for analyzing sets of two-way contingency tables. The proposed fixed-distance models differ from traditional latent class models in that the assumption of local stochastic independence is superseded by allowing interactions of the manifest variables within each class, which can be represented by a single association parameter. As an example, two data sets on eye color by hair color [collected in Caithness (N1 = 5,387) and Aberdeen (N2 = 22,361)] and fixed-distance models with up to six classes (three classes per data set) are considered, finally leading to satisfactory fit and rather simple interpretation.

Child↗

PubMed2003

The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes.

We have examined melanocortin-1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color, freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32-140) or weak r (OR = 5; 95% CI 3-11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild-type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk.

Alleles↗