Unification hypothesis of pigment dispersion syndrome

ArticleinTransactions of the American Ophthalmological Society 94:381-405; discussion 405-9 · February 1996with44 Reads
Source: PubMed

To synthesize recent findings regarding pigment dispersion syndrome in order to arrive at a hypothesis concerning the nature of an underlying genetic predisposition. The literature on the subject was reviewed and analyzed. Eyes with pigment dispersion syndrome differ from normal in that they have a larger iris, a midperipheral posterior iris concavity that increases with accommodation, a more posterior iris insertion, increased iridolenticular contact that is reversed by inhibition of blinking, possibly an inherent weakness of the iris pigment epithelium, and an increased incidence of lattice degeneration of the retina. A gene affecting some aspect of the development of the middle third of the eye early in the third trimester appears at the present time to be the most likely cause.

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    • "High intraocular pressure (IOP) is a major risk factor contributing to glaucoma [1] . Pigment dispersion syndrome (PDS) is a common condition that results in the dispersion of iris pigment into the anterior chamber (AC) [2,3]. The dispersed pigment accumulates within the ocular drainage structures, resulting in IOP elevation and glaucoma in some but not all individuals with PDS45678. "
    [Show abstract] [Hide abstract] ABSTRACT: The molecular mechanisms causing pigment dispersion syndrome (PDS) and the pathway(s) by which it progresses to pigmentary glaucoma are not known. Mutations in two melanosomal protein genes (Tyrp1b and GpnmbR150X) are responsible for pigment dispersing iris disease, which progresses to intraocular pressure (IOP) elevation and subsequent glaucoma in DBA/2J mice. Melanosomal defects along with ocular immune abnormalities play a role in the propagation of pigment dispersion and progression to IOP elevation. Here, we tested the role of specific immune components in the progression of the iris disease and high IOP. We tested the role of NK cells in disease etiology by genetically modifying the B6.D2-GpnmbR150X Tyrp1b strain, which develops the same iris disease as DBA/2J mice. Our findings demonstrate that neither diminishing NK mediated cytotoxic activity (Prf1 mutation) nor NK cell depletion (Il2rg mutation) has any influence on the severity or timing of GpnmbR150X Tyrp1b mediated iris disease. Since DBA/2J mice are deficient in CD94, an important immune modulator that often acts as an immune suppressor, we generated DBA/2J mice sufficient in CD94. Sufficiency of CD94 failed to alter either the iris disease or the subsequent IOP elevation. Additionally CD94 status had no detected effect on glaucomatous optic nerve damage. Our previous data implicate immune components in the manifestation of pigment dispersion and/or IOP elevation in DBA/2J mice. The current study eliminates important immune components, specifically NK cells and CD94 deficiency, as critical in the progression of iris disease and glaucoma. This narrows the field of possible immune components responsible for disease progression.
    Full-text · Article · Mar 2014 · BMC Genetics
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    • "Finally, it should be noted that studies have shown that there are several risk factors that may contribute to pigmentary dispersion glaucoma including large eye, age, sex, and race. For example it has been shown that pigmentary glaucoma is most commonly found in young, myopic, white males (Niyadurupola and Broadway, 2008; Ritch, 1996). A relative posterior position ofFig. "
    [Show abstract] [Hide abstract] ABSTRACT: The purpose of this work was to study in silico how iris root rotation due to spontaneous blinking alters the iris contour. An axisymmetric finite-element model of the anterior segment was developed that included changes in the iris contour and the aqueous humor flow. The model geometry was based on average values of ocular dimensions. Blinking was modeled by rotating the iris root posteriorly and returning it back to the anterior. Simulations with maximum rotations of 2°, 4°, 6°, and 8° were performed. The iris-lens contact distance and the pressure difference between the posterior and anterior chambers were calculated. When the peak iris root rotation was 2°, the maximum iris-lens contact increased gradually from 0.28 to 0.34mm within eight blinks. When the iris root was rotated by 6° and 8°, the pressure difference between the posterior and anterior chambers dropped from a positive value (1.23Pa) to negative values (-0.86 and -1.93Pa) indicating the presence of reverse pupillary block. Apparent iris-lens contact increased with steady blinking, and the increase became more pronounced as posterior rotation increased. We conclude that repeated iris root rotation caused by blinking could maintain the iris in a posterior position under normal circumstances, which would then lead to the clinically observed anterior drift of the iris when blinking is prevented.
    Full-text · Article · Jul 2012 · Journal of Biomechanics
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    • "Pigment dispersion is a feature of particular importance to the eye disease, pigment dispersion syndrome and it's potentially blinding sequelae, pigmentary glaucoma (Ritch, 1996). In this disorder, iridial pigment accumulates in ocular drainage structures and is accompanied by decreased aqueous humor outflow, increased intraocular pressure, and glaucoma. "
    [Show abstract] [Hide abstract] ABSTRACT: Spontaneous mutations altering mouse coat colors have been a classic resource for discovery of numerous molecular pathways. Although often overlooked, the mouse iris is also densely pigmented and easily observed, thus representing a similarly powerful opportunity for studying pigment cell biology. Here, we present an analysis of iris phenotypes among 16 mouse strains with mutations influencing melanosomes. Many of these strains exhibit biologically and medically relevant phenotypes, including pigment dispersion, a common feature of several human ocular diseases. Pigment dispersion was identified in several strains with mutant alleles known to influence melanosomes, including beige, light, and vitiligo. Pigment dispersion was also detected in the recently arising spontaneous coat color variant, nm2798. We have identified the nm2798 mutation as a missense mutation in the Dct gene, an identical re-occurrence of the slaty light mutation. These results suggest that dysregulated events of melanosomes can be potent contributors to the pigment dispersion phenotype. Combined, these findings illustrate the utility of studying iris phenotypes as a means of discovering new pathways, and re-linking old ones, to processes of pigmented cells in health and disease.
    Full-text · Article · Aug 2008 · Pigment Cell & Melanoma Research
    0Comments 16Citations
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