Intravitreal Implantation of Genetically Modified Autologous Bone Marrow-Derived Stem Cells for Treating Retinal Disorders.

A number of retinal degenerative diseases may be amenable to treatment with continuous intraocular delivery of therapeutic agents that cannot be delivered effectively to the retina via systemic or topical administration. Among these disorders are lysosomal storage diseases resulting from deficiencies in soluble lysosomal enzymes. Most cells, including those of the retina, are able to take up these enzymes and incorporate them in active form into their lysosomes.

A truncating mutation in ATP13A2 is responsible for adult-onset neuronal ceroid lipofuscinosis in Tibetan terriers.

A recessive, adult-onset neuronal ceroid-lipofuscinosis (NCL) occurs in Tibetan terriers. A genome-wide association study restricted this NCL locus to a 1.3Mb region of canine chromosome 2 which contains canine ATP13A2.

A missense mutation in canine CLN6 in an Australian shepherd with neuronal ceroid lipofuscinosis.

The childhood neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative diseases that are progressive and ultimately fatal. An Australian Shepherd that exhibited a progressive neurological disorder with signs similar to human NCL was evaluated. The cerebral cortex, cerebellum, and retina were found to contain massive accumulations of autofluorescent inclusions characteristic of the NCLs.

A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund.

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases characterized by progressive neurodegeneration and accumulation of autofluorescent storage granules. A 9-month-old Miniature Dachshund presented with NCL-like signs that included disorientation, ataxia, weakness, visual impairment, and behavioral changes. Neurons throughout the CNS contained autofluorescent lysosomal inclusions with granular osmiophilic deposit (GROD) ultrastructure characteristic of classical infantile NCL (INCL).

An ADAMTS17 splice donor site mutation in dogs with primary lens luxation.

Purpose: To identify the genetic cause of isolated canine ectopia lentis, a well-characterized veterinary disease commonly referred to as primary lens luxation (PLL) and to compare the canine disease with a newly described human Weill-Marchesani syndrome (WMS)-like disease of similar genetic etiology.

Methods: Genomewide association analysis and fine mapping by homozygosity were used to identify the chromosomal segment harboring the PLL locus. The resequencing of a regional candidate gene was used to discover a mutation in a splice donor site predicted to cause exon skipping.

RPE65 gene mutation prevents development of autofluorescence in retinal pigment epithelial phagosomes.

During senescence, autofluorescent lysosomal storage bodies known as lipofusin or age pigment accumulate in many post-mitotic types of cells. Among these cell types is the retinal pigment epithelium (RPE) of the mammalian eye. The mechanisms of lipofuscin formation and accumulation have been studied more extensively in the RPE than in any other cell type.

Retinal capillary basement membrane thickening in a porcine model of diabetes mellitus.

Purpose: Current animal models of diabetic microangiopathy, including diabetic retinopathy (DR), have substantial limitations. To determine whether the diabetic pig would provide an improved large animal model of DR, a 20-week porcine model of diabetic dyslipidemia that manifests appreciable macrovasculopathy was evaluated for development of retinal microvascular changes associated with diabetes mellitus (hereafter referred to as diabetes) in humans.

Methods: The effect of diabetes alone or in combination with high dietary fat intake on retinal capillary morphology was assessed.

Export of the siderophore enterobactin in Escherichia coli: involvement of a 43 kDa membrane exporter.

The enterobactin system for iron transport in Escherichia coli is well characterized with the exception of the mechanism of enterobactin secretion to the extracellular environment. Escherichia coli membrane protein P43, encoded by ybdA in the chromosomal region of genes involved in enterobactin synthesis, shows strong homology to the 12-transmembrane segment major facilitator superfamily of export pumps. A P43-null mutation was created and siderophore nutrition assays, performed with a panel of E.

Assessment of plasma carnitine concentrations in relation to ceroid lipofuscinosis in Tibetan Terriers.

Objective: To determine whether the late onset form of inherited ceroid lipofuscinosis (CL) in Tibetan Terriers is accompanied by low plasma carnitine concentrations prior to the appearance of clinical signs.

Animals: 129 healthy Tibetan Terriers, 12 Tibetan Terriers with CL, and 95 healthy purebred dogs of other breeds.

Procedure: After withholding food, blood samples were collected from all dogs into tubes containing EDTA.