Susan KIDSON - Academia.edu (original) (raw)

Papers by Susan KIDSON

Encyclopedia of the Eye, 2010

The ciliary body (CB) is supplied with blood from the anterior ciliary arteries (which arise from... more The ciliary body (CB) is supplied with blood from the anterior ciliary arteries (which arise from the four recti muscle arteries) and the long posterior ciliary arteries which traverse the interior. A complex arrangement of branches and anastomoses from these cells culminates circularly arranged vessels, including the episcleral arterial circle, the intramuscular circle of the ciliary muscle, and the major arterial circle (MAC). Each ciliary process receives blood from branches off the MAC, which follow a tortuous route through three vascular territories. Venules drain through the pars plana and exit via the vortex veins. CB vessels have wide lumens and are fenestrated, allowing production of aqueous humor. The complexity, density, and redundancy of vessels ensures consistent perfusion of the anterior segment.

Experimental eye research, Jan 9, 2016

Mutations in the FOXC1/Foxc1 gene in humans and mice and Bmp4 in mice are associated with congeni... more Mutations in the FOXC1/Foxc1 gene in humans and mice and Bmp4 in mice are associated with congenital anterior segment dysgenesis (ASD) and the development of the aqueous outflow structures throughout the limbus. The aim of this study was to advance our understanding of anterior segment abnormalities in mouse models of ASD using a 3-D imaging approach. Holistic imaging information combined with quantitative measurements were carried out on PECAM-1 stained individual components of the aqueous outflow vessels and corneal vasculature of Foxc1(+/-) on the C57BL/6Jx129 and ICR backgrounds, Bmp4(+/-) ICR mice, and wildtype mice from each background. In both wildtype and heterozygotes, singular, bifurcated and plexus forms of Schlemm's canal were noted. Of note, missing portions of the canal were seen in the heterozygous groups but not in wildtype animals. In general, we found the number of collector channels to be reduced in both heterozygotes. Lastly, we found a significant increase i...

The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology, 2004

The naked mole rat (Heterocephalus glaber) is a subterranean rodent whose eyes are thought to be ... more The naked mole rat (Heterocephalus glaber) is a subterranean rodent whose eyes are thought to be visually nonfunctional and as such is an ideal animal with which to pursue questions in evolutionary developmental biology. This report is the first in-depth study on the development and morphology of the naked mole rat eye. Using standard histological analysis and scanning and transmission electron microscopy, we describe the structural features of the eye. We further report on the morphological changes that accompany the development of this eye from neonate to adult and compare them with those that occur during mouse eye development. We observed numerous abnormalities in the shape and cellular arrangement of the structures of the anterior chamber, with notable malformations of the lens. Cell proliferation and cell death assays were conducted to investigate the possible causes of lens malformation. We found that neither of these processes appeared abnormal, indicating that they were not...

Gene, 1998

We have cloned and sequenced a chicken cDNA encoding an -DOPAchrome tautomerase (DCT) from an em... more We have cloned and sequenced a chicken cDNA encoding an -DOPAchrome tautomerase (DCT) from an embryonic melanocyte cDNA library. The chicken DCT gene encodes a deduced protein of 516 amino acids (aas) and shares 69.2% and 69.9% aa sequence identity with the deduced mouse and human DCT proteins, respectively. Northern blot hybridisation analysis reveals a DCT transcript of 3.5 kb in RNA from the retinal pigment epithelium (RPE) of chick embryos. Genomic Southern blot hybridisation analysis suggests that the chicken DCT gene consists of several introns and spans between 15 and 30 kb of the chicken genome. This study completes the sequencing of all the members of the chicken tyrosinase-related protein gene family and provides evidence that this gene family is conserved between avians and mammals.

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression, 1998

We have cloned a cDNA encoding an avian homologue of the mammalian brownr TYRP1 locus protein. Th... more We have cloned a cDNA encoding an avian homologue of the mammalian brownr TYRP1 locus protein. The chick Ž. tyrosinase-related protein-1 TRP-1 gene encodes a deduced protein of 535 amino acids, shares) 65% amino acid sequence identity with fish and mammalian TRP-1 proteins, and spans 5-11 kb of the chick genome. q 1998 Elsevier Science B.V.

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease that is characteri... more Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease that is characterised by ataxia and visual loss. It results from a degeneration of cerebellar Purkinje neurons and retinal photoreceptors caused by a polyglutamine repeat expansion in the ATXN7 gene, a component of the STAGA transcription co-activator complex. As with many neurodegenerative diseases, studies of pathogenesis have been hindered by a lack of disease-relevant models. To this end, we have generated the first induced pluripotent stem cells (iPSCs) from South African SCA7 patients, where the disease occurs at an unusually high frequency as a result of a founder effect. These iPSCs were capable of differentiation into neural and retinal cells, and showed evidence of a transcriptional phenotype affecting components of STAGA (ATXN7 and KAT2A) and the heat shock protein pathway (DNAJA1 and HSP70). Functionally, SCA7 iPSC-derived neurons exhibited more negative resting membrane potentials and increas...

Journal of Photochemistry and Photobiology B: Biology, 2008

Hypericin, the major component of St. John's Wort, absorbs light in the UV and visible ranges whe... more Hypericin, the major component of St. John's Wort, absorbs light in the UV and visible ranges whereupon it becomes phototoxic through the production of reactive oxygen species. Although photodynamic mechanisms (i.e. through endogenous photosensitizers) play a role in UVA phototherapy for the treatment of skin disorders such as eczema and psoriasis, photodynamic therapy employing exogenous photosensitizers are currently being used only for the treatment of certain forms of non-melanoma skin cancers and actinic keratoses. There are few reports however on its use in treating melanomas. This in vitro study analyses the phototoxic effect of UVA (400-315 nm)-activated hypericin in human pigmented and unpigmented melanomas and immortalised keratinocytes and melanocytes. We show that neither hypericin exposure nor UV irradiation alone reduces cell viability. We show that an exposure to 1 lM UVA-activated hypericin does not bring about cell death, while 3 lM activated hypericin induces a necrotic mode of cell death in pigmented melanoma cells and melanocytes and an apoptotic mode of cell death in non-pigmented melanoma cells and keratinocytes. We hypothesis that the necrotic mode of cell death in the pigmented cells is possibly related to the presence of melanin-containing melanosomes in these cells and that the hypericin-induced increase in reactive oxygen species leads to an increase in permeability of melanosomes. This would result in toxic melanin precursors (of an indolic and phenolic nature) leaking into the cytoplasm which in turn leads to cell death. Hypericin localisation in the endoplasmic reticulum in these cells shown by fluorescent microscopy, further support a disruption in cellular processing and induction of cell death. In contrast, this study shows that cells that do not contain melanosomes (non-pigmented melanoma cells and keratinocytes) die by apoptosis. Further, using a mitochondrial-specific fluorescent dye, we show that intracellular accumulation of hypericin induces a mitochondrial-associated caspase-dependent apoptotic mode of cell death. This work suggests that UVA is effective in activating hypericin and that this phototoxicity may be considered as treatment option in some cases of lentigo maligna or lentigo maligna melanoma that are too large for surgical resection.

Journal of Molecular Histology, 2006

Immunocytochemical identification of skin cells are difficult due to numerous endogenous autofluo... more Immunocytochemical identification of skin cells are difficult due to numerous endogenous autofluorescent components within the cell and the environment. This is particularly evident in hair follicles. This paper reports on a serendipitous modification to an existing method which results in a drastically reduced background fluorescence. Immediately after antigen retrieval, sections exposed to 0.3% hydrogen peroxide in methanol for 30 min at room temperature exhibited low background fluorescence, increased antigenicity and revealed quantifiable numbers of melanocytes. This method is applicable to both human and mouse melanocytes particularly in the hair follicle.

The Journal of experimental zoology, 1981

The tyrosinase activity of Himalayan mouse skin homogenates was measured over a range of temperat... more The tyrosinase activity of Himalayan mouse skin homogenates was measured over a range of temperatures using two sensitive radiometric assay--namely, (1) the measurement of 14C-tyrosine incorporation into melanin, and (2) the measurement of 3HOH released as a by-product of 3H-tyrosine hydroxylation. Results show that Himalayan tyrosinase is maximally active at temperatures well below normal body temperature (15 degree C to 25 degree C). These results are in support of Danneel's visual observations ('41) that "ferment" activity of Himalayan rabbit skin is absent at temperatures above 25 degree C. Further results suggest the presence of a tyrosinase inhibitor in Himalayan mouse skin. First, removal of a low molecular weight fraction from Himalayan skin homogenates resulted in an increase in tyrosinase activity. Second, recombination of the low molecular weight fraction to the homogenate from which it was originally separated resulted in a decrease in tyrosinase activi...

International Journal of Dermatology, 2007

Vitiligo is a depigmenting disease of uncertain aetio-pathogenesis. Although accepted as dogma, t... more Vitiligo is a depigmenting disease of uncertain aetio-pathogenesis. Although accepted as dogma, the question of whether melanocytes survive in vitiligo lesions has not been adequately resolved. Defining with greater accuracy the melanocyte status of lesions would contribute greatly towards the understanding of the etiology, progression and treatment of this disorder. We have therefore revisited this issue by carrying out a molecular screen for melanocytes in lesional skin using the sensitive and specific technique of reverse transcription PCR (RT-PCR) followed by Southern blotting. Biopsies from vitiligo lesions and normal skin were obtained from 15 patients. The RT-PCR was carried out using primers for tyrosinase and dopa-chrome tautomerase (DCT). To increase the sensitivity of detection, Southern-blot analysis of all PCR products was conducted. Southern-blot analysis indicated that three lesional samples were positive: one for tyrosinase, one for DCT, and one for both. Lesions yielding positive results had been present for between 2-5 years and were inactive, as defined by no disease progression within the last 3 months. Some vitiligo lesions showed evidence of melanocyte survival, even after some years. These results open the way for the possibility of using a range of melanocyte-specific markers for molecular staging of lesional status by quantitative RT-PCR. Such information would be extremely valuable for the appropriate selection and potential success of medical therapies.

Experimental eye research, 2014

The mouse eye has been used as a model for studies on the microanatomy of the outflow pathways bu... more The mouse eye has been used as a model for studies on the microanatomy of the outflow pathways but most of what is known comes from histological sections. These studies have focused mainly on the morphological features of the trabecular meshwork, Schlemm's canal and aqueous channels that link to the superficial episcleral vasculature. However, the anatomical architecture of the aqueous outflow vessels and their relationship to each other and to the general vascular circulation is not well understood. The aim of this study was to provide a detailed description of the microarchitecture of the aqueous outflow vessels and their relationship to the superficial limbal/episcleral vasculature throughout the entire limbus. The aqueous outflow vessels and blood and lymphatic vessels were imaged in PECAM-1 and LYVE-1 immunostained whole anterior segments of adult mice and three-dimensional (3-D) reconstructions of the optical sections were generated to reveal the aqueous, blood and lymphat...

The Journal of experimental zoology, 1979

The effect of temperature on pigment synthesis in adult and juvenile Himalayan mice was investiga... more The effect of temperature on pigment synthesis in adult and juvenile Himalayan mice was investigated. Since pigment synthesis only occurs in actively growing hair, adult mice were plucked to induce hair growth. The extent of darkening of the hair was recorded by photography against a reference scale. The presence of pigment granules in hair follicles was investigated histologically. Housing adult and juvenile mice at 15 degrees C results in the synthesis of pigment in growing hair follicles whereas housing at 30 degrees C results in the absence of pigment granules in the growing hair follicles.

Journal of the South African Veterinary Association, 2002

South African Medical Journal, 2012

Proceedings of the National Academy of Sciences, 1988

An early and a late histone H2B gene from the sea urchin Stronglyocentrotus purpuratus were linke... more An early and a late histone H2B gene from the sea urchin Stronglyocentrotus purpuratus were linked in a single plasmid and injected into the eggs of the sea urchin Lytechinus pictus. The levels of transcripts of injected early and late genes and of endogenous early genes were monitored during development by a ribonuclease protection assay. Transcripts of both the injected and endogenous early genes peaked during the blastula stage and decreased severalfold by the mesenchyme blastula stage. Transcripts of the injected late gene became detectable at the blastula stage and increased in amount subsequently, until at least the early gastrula stage, 28 hr after fertilization. Thus, the pattern of expression of the injected early and late H2B genes is similar to that of their endogenous counterparts. These results show that DNA sequences regulating the temporal pattern of early and late H2B gene expression must lie within the cloned DNA segments; i.e., within 600 base pairs of the early H2...

Pigment Cell Research, 1997

Tyrosinase is one of the key enzymes essential for melanogenesis. The control of its activity res... more Tyrosinase is one of the key enzymes essential for melanogenesis. The control of its activity rests in part at the level of transcriptional regulation. The 5' promoter regions of the human, mouse, chicken, quail, snapping turtle, and frog tyrosinase sequences have been isolated and the mechanisms regulating the activity of these sequences are beginning to be elucidated. This review provides an update on the following aspects of tyrosinase gene regulation: basal promoter elements that determine the site of transcription initiation for RNA polymerase II; the cis-acting elements and DNA-binding factors that mediate melanocyte-specific expression of the tyrosinase gene; promoter elements involved in the temporal control of tyrosinase gene expression; additional elements that may be required to achieve wild-type levels of gene expression; and specific elements that may be required for modulation of tyrosinase gene expression in response to humoral factors or external stimuli that are known to influence the amounts of melanin synthesized by fully differentiated melanocytes. The wild type expression of tyrosinase is the result of the interaction of many different factors and it is becoming evident that certain elements and factors play more than one role in this process.

Ophthalmic Paediatrics and Genetics, 1990

As the Alzheimer's disease process progresses in time measurements of cognitive functioning exhib... more As the Alzheimer's disease process progresses in time measurements of cognitive functioning exhibit nonlinearity. Multiphase models were used to quantify this nonlinearity for thirty-six well characterized individuals(∼12 observations per individual over ∼15 years in the study) by partitioning each into a healthy aging phase and a diseased phase. This enabled us to detail both the magnitude and timing that Alzheimer's disease alters different aspects of cognitive function. Estimation of these models was done using Bayesian methods. Eight different outcomes representing three areas of memory functioning(visual, verbal, working) were used to define a pattern of cognitive decline. The earliest phase change was found to be visual memory(∼6 years before diagnosis) and was followed by changes in verbal and working memory beginning roughly four years later.

Nutrition, 2013

Corticotropin-releasing factor (CRF) is implicated in stress-related gastrointestinal dysfunction... more Corticotropin-releasing factor (CRF) is implicated in stress-related gastrointestinal dysfunction, possibly causing gut dysfunction following trauma and surgery. We investigated plasma and intestinal tissue CRF levels and gut function in patients with traumatic shock or those undergoing elective abdominal surgery. In a prospective, parallel, observational study in a university hospital surgical intensive care unit (ICU), 8 shocked patients (systolic blood pressure &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;90 mmHg and/or acidosis and/or urine output &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 mL/kg/hr and/or requiring &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2 L of intravenous fluid resuscitation) undergoing small bowel resection during emergency laparotomy following abdominal injury and 17 stable patients undergoing elective hepatobiliary surgery were included if they required postoperative ICU management. Serial plasma and intestinal CRF was measured and postoperative gastric emptying and intestinal permeability were evaluated. Plasma CRF was significantly increased in the shocked patients compared with the elective surgery patients at all times. CRF peptide was quantified in intestinal tissue at similar levels in both groups. Intestinal permeability was increased and associated with shock and resuscitation fluid volume. Gastric emptying was retarded and correlated significantly with shock but not with plasma CRF. Delayed gastric emptying in shocked patients was associated with longer ICU stay. The novel finding is the presence of CRF in the small bowel of both elective and emergency gastrointestinal surgery patients with concomitant gastrointestinal dysfunction. Circulating CRF is associated with poor gastric emptying, which prolongs ICU stay, whereas shock significantly impairs gastric emptying and gut permeability.