Advanced glycation end product (AGE) accumulation on Bruch's membrane: links to age-related RPE dysfunction.

Purpose: Advanced glycation end products (AGEs) accumulate during aging and have been observed in postmortem eyes within the retinal pigment epithelium (RPE), Bruch's membrane, and subcellular deposits (drusen). AGEs have been associated with age-related dysfunction of the RPE-in particular with development and progression to age-related macular degeneration (AMD). In the present study the impact of AGEs at the RPE-Bruch's membrane interface was evaluated, to establish how these modifications may contribute to age-related disease.

Prediction and verification of miRNA expression in human and rat retinas.

Purpose: MicroRNAs (miRNAs) play a global role in regulating gene expression and have important tissue-specific functions. Little is known about their role in the retina. The purpose of this study was to establish the retinal expression of those miRNAs predicted to target genes involved in vision.

Retinopathy is reduced during experimental diabetes in a mouse model of outer retinal degeneration.

Purpose: Diabetic patients who also have retinitis pigmentosa (RP) appear to have fewer and less severe retinal microvascular lesions. Diabetic retinopathy may be linked to increased inner retinal hypoxia, with the possibility that this is exacerbated by oxygen usage during the dark-adaptation response. Therefore, patients with RP with depleted rod photoreceptors may encounter proportionately less retinal hypoxia, and, when diabetes is also present, there may be fewer retinopathic lesions.

Rod photoreceptor loss in Rho-/- mice reduces retinal hypoxia and hypoxia-regulated gene expression.

Purpose: This study was conducted to evaluate whether regions of the retinal neuropile become hypoxic during periods of high oxygen consumption and whether depletion of the outer retina reduces hypoxia and related changes in gene expression.

Methods: Retinas from rhodopsin knockout (Rho-/-) mice were evaluated along with those of wild-type (WT) control animals. Retinas were also examined at the end of 12-hour dark or light periods, and a separate group was treated with l-cis-diltiazem at the beginning of a 12-hour dark period.

Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene.

Purpose: Pigmented paravenous chorioretinal atrophy (PPCRA) is an unusual retinal degeneration characterized by accumulation of pigmentation along retinal veins. The purpose of this study was to describe the phenotype of a family with PPCRA, determine the mode of inheritance, and identify the causal mutation.

Methods: Ophthalmic examination was performed on seven family members and serially detailed in the proband over a 3-year period.

A novel diagnostic test detects a low frequency of the hemicentin Gln5345Arg variant among Northern Irish age related macular degeneration patients.

Purpose: Age related macular degeneration (AMD) is a common cause of severe vision loss. Identification of genes involved in AMD will facilitate early detection and ultimately help to identify pathways for treatment for this disorder. The A16,263G mutation in the HEMICENTIN-1 gene produces a non-conservative substitution of arginine for glutamine at codon 5345 which has been implicated in familial AMD.

Preparation of planar retinal specimens: verification by histology, mRNA profiling, and proteome analysis.

Purpose: Elucidation of the transcriptome and proteome of the normal retina will be difficult since it is comprised of at least 55 different cell types. However the characteristic layered cellular anatomy of the retina makes it amenable to planar sectioning, enabling the generation of enriched retinal cell populations. The aim of this study was to validate a reproducible method for preparing enriched retinal layers from porcine retina.

Sources of PDGF expression in murine retina and the effect of short-term diabetes.

Purpose: Progressive dysfunction and death of vascular smooth muscle cells and pericytes is a pathophysiological hallmark of diabetic retinopathy, although the underlying mechanisms behind this process remain ill-defined. The multifunctional peptide platelet-derived growth factor (PDGF) is known to act as an important survival factor for both of these vascular cell-types at times of physiological stress. The retinal cell source(s) of PDGF remain unknown.

Role of vascular endothelial growth factor and placental growth factors during retinal vascular development and hyaloid regression.

Purpose: Vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are members of a large group of homologous peptides identified as the VEGF family. Although VEGF-A is known to act as a potent angiogenic peptide in the retina, the vasoactive function of PlGF in this tissue is less well defined. This study has sought to elucidate the expression patterns and modulatory role of these growth factors during retinal vascular development and hyaloid regression in the neonatal mouse.

Application of in silico positional cloning and bioinformatic mutation analysis to the study of eye diseases.

A vast amount of DNA and protein sequence is now available and a plethora of programs have been developed to analyse the data. The bewildering variety of analyses that can be performed via the World-Wide Web can deter researchers from applying bioinformatics to augment their traditional genetic research. Focusing on the inherited eye diseases, this paper provides a guide to the appropriate software required for identification of candidate genes through to the detection and analysis of mutations.

Identification of an IMPDH1 mutation in autosomal dominant retinitis pigmentosa (RP10) revealed following comparative microarray analysis of transcripts derived from retinas of wild-type and Rho(-/-) mice.

Comparative analysis of the transcriptional profiles of approximately 6000 genes in the retinas of wild-type mice with those carrying a targeted disruption of the rhodopsin gene was undertaken by microarray analysis. This revealed a series of transcripts, of which some were derived from genes known to map at retinopathy loci, levels of which were reduced or elevated in the retinas of Rho(-/-) mice lacking functional photoreceptors. The human homologue of one of these genes, encoding inosine monophosphate dehydrogenase type 1 (IMPDH1), maps to the region of 7q to which an adRP gene (RP10) had previously been localized.