Search PubMed⌕ Search

Biomedical subjects

I M MacDonald

Publications and source records attributed to I M MacDonald.

At least 37 records · Page 2Linked to original sources
PubMed1996

Mutation analysis in Canadian families with choroideremia.

Choroideremia (CHM) is an X-linked heritable progressive dystrophy of the choroid and retina. The condition predominantly affects males beginning in early childhood and eventually results in blindness after a period of 30-40 years. The CHM gene was localized to Xq21 and cloned in the past few years. The gene encodes for Rab escort protein-I, a protein involved in the isoprenylation of intracellular proteins. With the isolation of the gene, a number of mutations have been identified in patients affected by CHM using molecular techniques. Our group reports the characterization of mutations in four Canadian families affected by CHM. In addition, an intragenic polymorphism was identified in exon 5. Finding the mutations in these families will result in accurate predictive testing for carriers, avoid unnecessary repeated examination of at-risk individuals, and add to our understanding of the cause of this disorder.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Effect of retinoic acid on wound healing of laser burns to porcine retinal pigment epithelium.

OBJECTIVE: To determine the effect of retinoic acid on wound healing of laser burns to explants of porcine retinal pigment epithelium (RPE). DESIGN: With the help of a mirrored attachment to a Coherent argon laser, laser burns (spot size 100 mu, power 500 mW, duration 0.2 seconds) were performed in 12 explants. The explants were then cultured in the presence (six explants) or absence (six explants) of 1 microM retinoic acid. Two explants in either group were recovered 4, 8 and 12 days after treatment for histologic study and scanning electron microscopy. OUTCOME MEASURE: Mean burn area remaining after culture. RESULTS: The area of wound remaining unhealed in the presence of retinoic acid was significantly larger than the area of wound remaining unhealed in the absence of retinoic acid at each time point. CONCLUSIONS: Retinoic acid inhibited wound healing of laser burns to porcine RPE. This effect may illustrate a role for retinoic acid in the pharmacotherapy of proliferative disorders.

Animals↗
PubMed1995

Mutation of the PAX6 gene in patients with autosomal dominant keratitis.

Autosomal dominant keratitis (ADK) is an eye disorder chiefly characterized by corneal opacification and vascularization and by foveal hypoplasia. Aniridia (shown recently to result from mutations in the PAX6 gene) has overlapping clinical findings and a similar pattern of inheritance with ADK. On the basis of these similarities, we used a candidate-gene approach to investigate whether mutations in the PAX6 gene also result in ADK. Significant linkage was found between two polymorphic loci in the PAX6 region and ADK in a family with 15 affected members in four generations (peak LOD score = 4.45; theta = .00 with D11S914), consistent with PAX6 mutations being responsible for ADK. SSCP analysis and direct sequencing revealed a mutation in the PAX6 exon 11 splice-acceptor site. The predicted consequent incorrect splicing results in truncation of the PAX6 proline-serine-threonine activation domain. The SeyNeu mouse results from a mutation in the Pax-6 exon 10 splice-donor site that produces a PAX6 protein truncated from the same point as occurs in our family with ADK. Therefore, the SeyNeu mouse is an excellent animal model of ADK. The finding that mutations in PAX6 underlie ADK, along with a recent report that mutations in PAX6 also underlie Peters anomaly, implicates PAX6 broadly in human anterior segment malformations.

DNA-Binding Proteins↗
PubMed1995

Effect of retinoic acid on expression of transforming growth factor-beta by retinal pigment epithelial cells in culture.

OBJECTIVE: To study the effect of retinoic acid on the expression of transforming growth factor-beta (TGF-beta) by human retinal pigment epithelial (RPE) cells in culture. MAIN OUTCOME MEASURES: Expression of TGF-beta 1 by RPE cells after 24 hours in culture at the messenger RNA level (Northern analysis) and the protein level (enzyme-linked immunosorbent assay [ELISA]). RESULTS: On the basis of cell morphology, growth characteristics and the results of immunohistochemical studies, we concluded that the cells used in these experiments were RPE in origin. Immunohistochemical studies confirmed TGF-beta 1 expression by the RPE cells in culture. Densitometry showed that retinoic acid reduced the level of TGF-beta 1 mRNA expression by 41% compared with control samples. ELISA showed that retinoic acid inhibited TGF-beta expression when compared with the baseline level of TGF-beta in media from RPE cells in culture. CONCLUSIONS: These findings may have implications for the pharmacotherapy of proliferative vitreoretinopathy.

Blotting, Northern↗
PubMed1994

Molecular genetics of inherited eye disorders.

In the past 10 y, there have been considerable advances in the mapping, isolation, and characterization of many genes for important ocular conditions: retinitis pigmentosa, Norrie disease, Waardenburg syndrome, choroideremia, aniridia, retinoblastoma, and others. The candidate gene approach has now supplemented classical linkage studies and positional cloning in the investigation of ocular disorders. Developmentally expressed genes and animal models have provided insights as to the etiology of other disorders. With this knowledge at hand, genetic counselling for heritable eye diseases has been greatly improved.

Animals↗
PubMed1993

Identification and partial characterization of a candidate gene for X-linked retinopathies using a lateral approach.

Using library to library cross-screening we have identified a number of genomic clones that harbor X-linked sequences expressed in the human choroid/retina. We describe the characterization of one of these, designated XEH.8 (DXS542), which is localized to Xp11.3-q12. Isolation, partial sequencing, and Northern analysis of the cognate cDNA (XEH.8c), has shown that the cDNA has some homology to the dystrophin gene and hybridizes to a 10-kb mRNA present in the choroid and retina but not in fibroblasts. This expressed sequence maps to the same region of the X chromosome as several known X-linked ophthalmic diseases, including Norrie disease, retinitis pigmentosa 2, congenital night blindness and Aland Island eye disease.

Amino Acid Sequence↗
PubMed1992

Cell culture of macular epiretinal membranes.

To attempt to differentiate the cells of origin in epiretinal membranes, cells were cultured from an idiopathic epiretinal membrane and an epiretinal membrane that formed after successful repair of a retinal detachment. The cells exhibited a variety of forms. When the cells from the idiopathic epiretinal membrane were incubated with melanin from donor eyes a population of small cells accumulated the pigment, but the large, flat cells did not. The epiretinal membrane was not composed of a single cell type. Although a population of cells exists within epiretinal membranes, no one cell type could be identified as the cell type of origin.

Aged↗
PubMed1991

Corneal endothelial decompensation after argon laser iridotomy.

Focal corneal edema overlying the site of argon laser iridotomy followed by generalized corneal decompensation developed in six eyes of five patients. The average interval between the iridotomy and the development of focal edema was 3 years, with generalized edema appearing an average of 3.5 months later. Light, scanning and transmission electron microscopy of tissue removed at the time of corneal transplantation showed abnormalities characteristic of Fuchs' dystrophy in two patients. Possible contributing factors include episodes of intraocular pressure elevation, cornea guttata and the use of high total amounts of energy during laser iridotomy.

Argon↗
PubMed1989

Growth and development in thanatophoric dysplasia.

Two cases of prolonged survival of thanatophoric dysplasia are presented, in which ventilatory support was initiated in the neonatal period because of respiratory distress. Both patients required a ventriculoperitoneal shunt for hydrocephalus and had decompression of the posterior fossa. The history of each patient has been characterized by profound developmental delay and dramatic growth failure.

Arm↗
PubMed1989

Scheie's syndrome. An ultrastructural analysis of the cornea.

The histopathology of a corneal graft specimen obtained from a patient with Scheie's syndrome (systemic mucopolysaccharidosis, type IS) is described with particular emphasis on the ultrastructural findings. Numerous vacuoles containing fibrillogranular material were found in the corneal epithelial cells, the keratocytes, and the endothelial cells. The basement membrane of the epithelium contained frequent breaks and peg-like undulations, and Bowman's layer was markedly attenuated. Fibrous long-spacing (FLS) collagen featured prominently in the stroma. Descemet's membrane was normal. The findings of a markedly attenuated Bowman's layer and FLS collagen may be abnormalities specific to Scheie's syndrome resulting from the altered glycosaminoglycan composition of the extracellular matrix.

Adolescent↗
PubMed1989

Corneal toxic changes after cataract extraction.

Over an 18-month period 10 patients (12 eyes) presented with severe corneal toxic changes after cataract extraction. Defined stages in the keratopathy included punctate epithelial keratopathy, pseudodendrite, central epithelial ulcer and central stromal ulcer. Periods of up to 13 months were required for resolution of the defects. Axial scarring and nonhealing epithelial defects resulted in a final visual acuity of counting fingers and hand movement in two patients. We believe that exposure during the postoperative period to benzalkonium chloride contained in ophthalmic medications represents the most likely cause of the toxic changes and that no single ophthalmic medication can be held responsible. The past ocular histories of the patients included chronic open-angle glaucoma, dry eye syndrome and anterior membrane dystrophy. Prior exposure to benzalkonium-containing antiglaucoma medications, tear film deficiencies or abnormalities of epithelial adhesion may have predisposed the corneas in these patients to the development of benzalkonium-related toxic changes.

Benzalkonium Compounds↗