HMG CoA reductase inhibitors (statins): do they have a role in age-related macular degeneration?

Age-related macular degeneration is a progressive late onset disease affecting central vision. It is the leading cause of irreversible blindness in developed countries, and with the aging population the problem is increasing. Current treatment options are limited to the late stage of the disease when central vision is already under great threat, and even new treatments make little impact on the rate of blindness.

Analysis of optineurin (OPTN) gene mutations in subjects with and without glaucoma: the Blue Mountains Eye Study.

Background: The optineurin (OPTN) gene has been reported to possess both causal as well as risk-associated alleles for open-angle glaucoma. However, these findings have so far only been reported in family and clinic based studies. The aim of this study was to investigate the spectrum of mutations and gene variants in OPTN that might be present in people with glaucoma from a population-based study, the Blue Mountains Eye Study (BMES).

Association of the M55L and Q192R paraoxonase gene polymorphisms with age-related macular degeneration.

Purpose: To investigate the reported association of the two single-nucleotide polymorphisms (SNPs) of the paraoxonase gene (PON1), Met-Leu 55 (M55L) and Gln-Arg 192 (Q192R), in individuals of Anglo-Celtic descent who have age-related macular degeneration (AMD).

Design: Case-control association study.

Methods: Sixty-two individuals with late (end-stage) AMD and 115 control subjects (without AMD) were included in this study.

Analysis of the EFEMP1 gene in individuals and families with early onset drusen.

Aims: Age-related macular degeneration (AMD) is considered a complex genetic disease, although the genetic influences are not yet fully understood. Genetic analysis is hampered by the late onset of disease and the difficulty in obtaining multigenerational families. To investigate this problem further we studied our population of early onset drusen cases.

Prenatal screening and the reduction of birth defects in populations.

Objectives: Birth defects occur in populations in 3-5% of births. This paper assesses whether population-wide screening programmes for pregnant women would be likely to result in major decreases in the prevalence of birth defects.

Method: Relevant literature on this question is reviewed and synthesized.

The epsilon2 and epsilon4 alleles of the apolipoprotein gene are associated with age-related macular degeneration.

Purpose: To date, of all the genes studied in relation to age-related macular degeneration (AMD), the alleles of the apolipoprotein (apoE) gene have been the most consistently associated with disease. However, not all apoE studies have found an association, and among these the associations differ. The current study was conducted to investigate further the association of this gene in AMD.

The Human Genome Project, genetics and health.

Three main reasons why a genetic approach is unlikely to be a solution to common diseases in the foreseeable future are discussed. The first is the great importance of environmental circumstances in determining health, the second reason is the great complexity of gene/gene, gene/environment interactions, and the third reason is human behavior with regard to compliance with medical recommendations. Since particular interests are likely to push for a genetic approach to disease, there will be a need to protect the public interest so that premature and inappropriate use of genetics is not made, and so that a balanced opportunity to better the health of all is not missed.

Analysis of 15 primary open-angle glaucoma families from Australia identifies a founder effect for the Q368STOP mutation of myocilin.

Primary open-angle glaucoma (POAG) is a leading cause of blindness in the world. A number of mutations in the myocilin gene have been identified that predispose to glaucoma. The most frequent of these is the Glutamine368STOP (Q368STOP) mutation.

Analysis of the Arg345Trp disease-associated allele of the EFEMP1 gene in individuals with early onset drusen or familial age-related macular degeneration.

Background: A single base change within the EFEMP1 gene has been associated with malattia leventinese and Doyne honeycomb retinal dystrophy, two dominantly inherited macular diseases with early onset drusen. The aim of this study was to determine whether the same disease allele was also associated with other forms of early onset drusen or familial cases of age-related macular degeneration.

Methods: Thirteen index cases of early onset drusen together with 15 other family members were examined.

Identification of genetic susceptibility to common diseases: the case for regulation.

There is, and will continue to be, pressure to disseminate and market population-wide availability of genetic susceptibility tests for common, complexly determined diseases. Many of the claims for such genetic screening tests are made by parties who stand to gain: laboratories, service providers, biotechnology firms, scientists working in genetics. Despite the fact that there is little or no evidence to support the claims of benefit, the current lack of appropriate regulation means there is a danger that promotion and advertising will nevertheless be successful in marketing such testing.

Nerve growth factor expression and innervation of the painful intervertebral disc.

Following a previous description of nociceptive nerve fibre growth into usually aneural inner parts of painful intervertebral disc (IVD), this study has investigated whether nociceptive nerve ingrowth into painful IVD is stimulated by local production of neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin, nerve growth factor (NGF), and its high- and low-affinity receptors trk-A and p75, respectively, in painful IVD excised for the management of low back pain. IVD from patients with back pain were of two types: those that when examined by discography reproduced the patient symptoms (pain level IVD) and those that did not (non-pain level IVD).

Expression of chondrocyte markers by cells of normal and degenerate intervertebral discs.

Aims: To investigate the phenotype of cells in normal and degenerate intervertebral discs by studying the expression of molecules characteristic of chondrocytes in situ.

Methods: Human intervertebral discs taken at surgery were graded histologically, and classified on this basis as normal or degenerate. Eighteen of each type were selected, and in situ hybridisation was performed for the chondrocytic markers Sox9 and collagen II using (35)S labelled cDNA probes.

Generating mouse models of retinal disease using ENU mutagenesis.

We used the chemical mutagen, N-ethyl-N-nitrosourea, to induce random point mutations in the germline of the mouse strain C57BL/6 in order to generate models of retinal diseases. 1163 mutagenised first generation mice produced using this approach were examined for eye abnormalities. Approximately one-third (412) presented with some form of ocular abnormality.