Pigmentary mosaicism and specific forms of phylloid hypoand hypermelanosis

Pigmentary mosaicism is proposed to encompass all pigment anomalies caused by chromosomal mosaicism. The concept includes, not only pigment anomalies following the lines of Blaschko, but also pigmentary disorders with phylloid, checkerboard and patchy pigmentation without midline separation. The representative disorders are hypomelanosis of Ito(pigmentary mosaicism of hypopigmented or Ito type), linear and whorled nevoid hypermelanosis(pigmentary mosaicism of hyperpigmented type), pigmentary mosaicism of hypopigmented and hyperpigmented type, and phylloid hypo- and hypermelanosis. Pigmentary mosaicism is nowadays recognized as a pigmentary disorder caused by somatic chromosomal abnormalities disrupting or accelerating the function of pigmentary genes. Affected individuals with pigmentary mosaicism commonly have multiple congenital abnormalities, developmental delays and/or mental retardation. However, the complication is not a syndrome because functional loss or acquisition due to various chromosomal abnormalities induces pigment abnormalities and specific complications. Cytogenetic abnormalities, including polyploidy, aneuploidy, deletions, insertions and translocations, are associated with almost any chromosome and tissue-limited mosaicism for chromosome abnormalities. Cytogenetic find-ings in cases with the phylloid pattern demonstrate the obvious causal relationship between phylloid hypomelanosis and mosaic trisomy 13. The pattern of cutaneous mosaicism depends on the trajectory of migration and proliferation during embryogenesis. The chromosomal regions of hot breakpoints in pigmentary mosaicism may contain pigmentation-associated genes. The accumulation of relationships between cases and chromosomal analyses may provide the opportunity to identify and understand the pigmentation-associated genes because more than 800 phenotypic alleles are known in the mice models of pigmentary anomalies and not all color loci have been identified. Here, we summarize the clinical features of pigmentary mosaicism and specific forms of phylloid hypo- and hypermelanosis.

The Role of Notch Signaling in Genetic Reticular Pigmentary Disorders

Notch signaling is an essential conserved mechanism through local cell interactions.It regulates cell differentiation,proliferation,and apoptotic,influencing organ formation and morphogenesis.Notch signaling plays a vital role in both development of melanocyte during embryogenesis and maintenance of melanocyte stem cells.POFUT1,POGLUT1,ADAM10,presenilin enhancer-2,and nicastrin genes are pathogenic genes of genetic reticular pigmentation diseases Dowling-Degos disease,reticulate acropigmentation of Kitamura,and acne inversa with pigment abnormalities separately.And they are all vital genes in Notch signaling pathway.This group of pigmentary diseases have similarities and overlaps in clinical manifestations and pathological characteristics.We review the essential role of Notch signaling in genetic reticular pigmentary disorders,and discuss the underlying mechanisms behind dysfunction of melanocyte induced by gene mutations in Notch signaling.

Long-term Efficacy of Trabeculectomy on Chinese Patients with Pigmentary Glaucoma： A Prospective Case Series Observational Study

Background： Though trabeculectomy is often performed on patients with medically refractive pigmentary glaucoma （PG）, the clinical outcomes of surgical treatment on PG remain unknown. The aim of this study was to summarize the long-term efficacy and safety of trabeculectomy on PG. Methods： This was a prospective case series observational study. Eighteen consecutive PG patients were followed up for 8 years after trabeculectomy from May 2006 to April 2007. Visual acuity （VA）, best-corrected visual acuity （BCVA）, slit lamp biomicroscopy, intraocular pressure （lOP） measurement, Humphrey visual field analysis （VFA）, and stereoscopic funduscopy were performed on admission and every 6 months after the surgery. Postoperative lOP, VA, BCVA, VFA, adjunctive anti-glaucoma medication, treatment-related side-effects, changes in blebs, and main clinical findings in the anterior segment of PG were recorded and compared with the baseline. Results： Eighteen PG eyes from 18 patients, with average preoperative IOP of 34.5±4.7 mmHg （range： 21 47 mmHg, 1 mmHg=0.133 kPa） were enrolled in this study. All enrolled patients completed the follow-up visits and required examinations. Eight years after trabeculectomy, all surgical eyes （18/18） had satisfactory IOP control with an average of 13.7 -~ 2.5 mmHg （range： 9-19 mmHg）, which was significantly lower than baseline （P - 0.001 ）. Majority （15/18） of the PG eyes had stable VA, BCVA, VFA, and optic disc cupping parameters. Functional blebs still existed in 12/18 of the PG eyes at the last follow-up visit. Unanimously, pigmentation in the anterior segment attenuated with time after surgical treatment. No severe side-effects were recorded in any of the surgical eyes. Conclusions： All surgical PG eyes in this study had satisfactory lOP control 8 years after the surgery with well-preserved visual function. The long-term efficacy and safety of trabeculectomy are promising in PG patients.

Highlights in pathogenesis of vitiligo

Vitiligo is a common pigmentary disorder. Many studies across decades and all over the world have attempted to illustrate the pathogenesis behind it; however, the pathogenesis of vitiligo remains elusive. This review article, we present the findings behind the most and updated theories behind this psychologically debilitating and disfiguring disease. The discussion begun with the role of genetic predisposition followed by neural theory first proposed in the 1950 s. Wehighlight the autoimmune hypothesis, followed by the reactive oxygen species model, zinc-α2-glycoprotein deficiency hypothesis, viral theory, intrinsic theory and biochemical, molecular and cellular alterations accounting for loss of functioning melanocytes in vitiligo. Many theories were elaborated to clarify vitiligo pathogenesis. It is a multifactorial disease involving the interplay of several factors. Future research is needed to clarify the interaction of these factors for better understanding of vitiligo pathogenesis and subsequent successful treatment.

Application of pulsed chemical vapor deposition on the SiO_(2)-coated TiO_(2) production within a rotary reactor at room temperature

Pulsed chemical vapor deposition(P-CVD)is a promising technology for the surface modification of TiO_(2) particles.For the scale-up application of P-CVD,a custom-designed rotary reactor and corresponding coating process at room temperature was developed in the present work.The obtained SiO_(2)-coated TiO_(2) particles were characterized by various measures including high-resolution transmission electron microscope,Fourier transform infrared spectroscopy,X-ray diffraction,etc.The results illustrated that the SiO_(2) films with a thickness of(3.7±0.7)nm were successfully deposited onto the surface of TiO_(2) particles.According to the dye degradation tests and acid solubility measurement,the deposited film can effectively inhibit the photocatalytic activity and enhance the weatherability of the TiO_(2) particles.Zeta potential measurements showed that the SiO_(2)-coated TiO_(2) is possible to be stably dispersed in the pH range of 6.9–11.6.The coating process made the whiteness of TiO_(2) particles decreased slightly but still sufficient(97.3±0.1)for application.Furthermore,the properties of the TiO_(2) particles coated by PCVD were compared with the particles coated by traditional wet chemical deposition.It is shown that the P-CVD can produce thinner but denser films with better photoactivity suppression performance.The developed coating process within the rotary reactor was proved practically feasible and convenient for the scale-up production of SiO_(2)-coated TiO_(2) via P-CVD.

Retinal ganglion cell death in a DBA/2J mouse model of glaucoma Microglial activation and intraocular pressure

BACKGROUND： Retinal microglia has been shown to reactivate in a murine model of pigmentary glaucoma. However, the relationship between microglial activation and intraocular pressure （lOP） elevation and retinal ganglion cell （RGC） death is still unclear. OBJECTIVE： To verify that microglial activation and tumor necrosis factor alpha （TNF-α） expression is involved in RGC death with elevated lOP and prolonged time of glaucomatous optic nerve lesion in a DBA/2J mouse model of glaucoma. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed at the Peking University Third Hospital, Peking University Eye Center, China between December 2006 and May 2008.MATEFIiALS： DBA/2J mice and C57BL/6J mice （Jackson Laboratory, USA）, rat anti-mouse CD11 b monoclonal antibody （Serotec, UK）, and goat anti-TNF-α polyclonal antibody （Sigma, USA） were used in this study.METHODS： A total of 100 female, DBA/2J mice at 3, 6, 9, 12, and 14 months of age （20 mice per age group） were used for the glaucoma model, and 18 C57BL/6J mice at 3, 9, 14 months of age （6 mice per age group） were used as normal controls. The anterior segment of the eye was observed using a slit-lamp biomicroscope, lOP was measured using a microneedle system. Morphology and number of retinal microglia were observed using immunohistochemistry. RGCs were quantified using Nissl staining. Co-localization of TNF-α and microglia was observed using double-labeling immunofluorescence. Excavation of the optic nerve head was observed utilizing hematoxylin-eosin staining. MAIN OUTCOME MEASURES： The following parameters were measured： lOP levels, numbers of RGCs and activated microglia, and TNF-α expression. RESULTS： In 6-month-old DBA/2J mice, dispersed pigment was observed, and some mice developed increased IOP. At 9 months of age, lOP levels reached a peak. In 3-month-old DBA/2J mice, microglia were activated. In 6-month-old DBA/2J mice, the number of activated microglia was significantly increased and migrated to the outer retinal layer. In 9-month-old mice, TNF-a expression was co-localized with microglia. Significant RGC loss occurred in mice aged 9 to 14 months, with the presence of optic nerve fiber loss and optical nerve head excavation, lOP returned to normal levels at 12 months of age, but microglia remained activated, which was consistent with RGC loss. CONCLUSION： Retinal microglial activation was partially attributed to increased lOP. Activated microglia might be mainly responsible for RGC loss. TNF-α expression was evident in the inner retinal layer. However, the relationship between TNF-α and RGC loss remains poorly understood.

Effect of shRNA Inhibiting HIF1α Gene on TIMP1 Expression in RPE Cells

Small hairpin RNA （shRNA） was used to silence the HIF1α gene in human retinal pigment epithelial cells （RPE） under hypoxia in order to observe the effect of gene silencing on the expression of matrix metalloproteinase tissue inhibitor 1 （TIMP1）. By using chemical hypoxic inducer CoCl2 to mimic RPE hypoxic environment, shRNA against the targeting region of HIF1α mRNA sequence was synthesized by a method of in vitro transcription, and the HIF1α was interfered in RPE cultured under hypoxia （induced by 150 μmol/L CoCl2 ）. RT-PCR was employed to detect the expression of HIF1α and TIMP1. The expression levels of HIF1α and TIMP1 were measured by using Western blotting. The results showed that after the RPE were transfected with specific shRNA against HIF1α mRNA, RT PCR revealed that under hypoxia, the efficacy of HIF1α gene silencing in RPE was 83.4 %. Western blotting revealed that the expression levels of HIF1α protein was dramatically dropped. In addition, RT-PCR results demonstrated that the expression of TIMP1 mRNA was decreased by 28.9 %, and the expression levels of TIMP1 protein were also significantly reduced by Western blotting. It was suggested that shRNA targeted against HIF1α mRNA could effectively silence the HIF1α gene, subsequently effectively inhibit the hypoxia-induced up-regulation of TIMP1.

Platycladus orientalis shells promote melanogenesis via p38,AKT and Wnt/β-catenin signaling pathways

Background:Platycladus orientalis,which has been employed in traditional Chinese medicine for cool blood,antibacterial,promotion of hair growth and therapy of poliosis for centuries.However,there have been few reports focusing on Platycladus orientalis shells treating pigmentary disorders.Methods:In present study,gas chromatography–mass spectrometry was applied to analyzing the volatile composition of Platycladus orientalis shells and cellular metabolism.Experiments in vivo were carried out to evaluate the effect of Platycladus orientalis shells treating pigmentation disorders in C57BL/6J mice.Results:Our results indicated that cedrol occupied the largest percentage in Platycladus orientalis shells(17.1%).Meanwhile,Platycladus orientalis shells up-regulated the content of palmitic acid and increased melanin content and tyrosinase activity.Its mechanism possibly involved in the inhibiting phosphorylation of AKT and β-catenin,increasing phosphorylation of p38 to promote microphthalmia-associated transcription factor expression.The animal experiment also proved that Platycladus orientalis shells promoted melanogensis and hair blacken in C57BL/6J mice.Conclusion:All in all,Platycladus orientalis shells potentially promoted melanogenesis in vitro and in vivo.Cedrol was regarded as the main active substance in Platycladus orientalis shells.Therefore,it could be used for treatment of pigmentary disorders under safe concentration in the prospective application.

Xeroderma pigmentosa with ocular association: Case report

Xeroderma pigmentosum is a rare, autosomal recessive disease caused by a defect in DNA repair. Patients with xeroderma pigmentosum often have cutaneous and ocular sun sensitivity, freckle-like skin pigmentation, multiple skin and eye cancers, and, in some patients, progressive neurodegeneration. Xeroderma pigmentosum predominantly affects the ultraviolet (UV) exposed ocular surface, resulting in eyelid atrophy and cancers, corneal dryness, exposure keratopathy, and conjunctival tumors. General features included parental consanguinity (40%), familiarity (60%), onset of symptoms in the first 2 years (50%), malignant skin neoplasms (60%), and carcinoma of the tongue (20%). Among the ocular features, 50% of patients presented with photophobia. Lid freckles or atrophic skin lesions were seen in all patients. Lower lid tumours were seen in 30%, chronic conjunctival congestion in 40%, corneal opacification in 40%, squamous cell carcinoma of limbus in 20%, bilateral pterygium in 40%, and visual impairment in 50%. We report the clinical history and ocular pathology of a boy who is having xeroderma pigmentosum with ocular manifestations. The ophthalmic manifestations of xeroderma pigmentosum are discussed and reviewed with respect to this report and other cases in the literature. These cases illustrate the role of DNA repair in protection of the eyes from UV damage and neuron degeneration of the retina.

Effects of the precursor size on the morphologies and properties of γ-Ce_2S_3 as a pigment

Ceria spheres with different sizes and sulfurized products with corresponding morphology were prepared by hydro-thermal and gas-solid reaction method at 600-800℃ under CS2 atmosphere for a short time, respectively. Dimensional effect in preparation ofγ-Ce2S3 was firstly investigated by means of techniques such as scanning electron microscopy （SEM）, X-ray dif-fraction （XRD）, thermal gravimetric analysis （TGA） and spectrophotometer. The results showed that when ceria nanoparticles with small size were used as precursors, theγ-Ce2S3 could be prepared at the lower temperature and the badly sintered products were obtained; when ceria nanoparticles with large size were employed as precursors, pureγ-Ce2S3 was difficultly obtained even if the temperature was up to 800℃ and the products tended to keep their original size. The heat-resistance property of theγ-Ce2S3 with large size was better than the smaller one, and the pureγ-Ce2S3 prepared from precursor with small size had a good pigmen-tary performance.