Mutation screen of beta-crystallin genes in 274 patients with age-related macular degeneration.

Purpose: The crystallin family of proteins comprise the main structural proteins of the vertebrate lens and have been classified into alpha-, beta-, and gamma- families. Several of the beta-crystallin proteins have been detected in the retina where they are each localized to different compartments of rod and cone photoreceptors. Functionally, beta-crystallins have been implicated in the protection of the retina from intense light exposure.

Light-evoked responses of the retinal pigment epithelium: changes accompanying photoreceptor loss in the mouse.

Mutations in genes expressed in the retinal pigment epithelium (RPE) underlie a number of human inherited retinal disorders that manifest with photoreceptor degeneration. Because light-evoked responses of the RPE are generated secondary to rod photoreceptor activity, RPE response reductions observed in human patients or animal models may simply reflect decreased photoreceptor input. The purpose of this study was to define how the electrophysiological characteristics of the RPE change when the complement of rod photoreceptors is decreased.

Proteomic and genomic biomarkers for age-related macular degeneration.

Toward early detection of susceptibility to age-related macular degeneration (AMD), we quantified plasma carboxyethylpyrrole (CEP) oxidative protein modifications and CEP autoantibodies by ELISA in 916 AMD and 488 control donors. Mean CEP adduct and autoantibody levels were elevated in AMD plasma by ∼60 and ∼30%, respectively, and the odds ratio for both CEP markers elevated was ∼3-fold greater in AMD than in control patients. Genotyping was performed for AMD risk polymorphisms associated with age-related maculopathy susceptibility 2 (ARMS2), high-temperature requirement factor A1 (HTRA1), complement factor H (CFH), and complement C3.

Protective effect of paraoxonase 1 gene variant Gln192Arg in age-related macular degeneration.

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness among older adults, in which oxidative damage may play a pivotal role. Paraoxonase 1 (PON1) protects against oxidative damage and has been evaluated for its involvement in aging diseases including AMD. This study investigated whether PON1 gene polymorphisms associate with AMD.

Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers.

Age-related macular degeneration (AMD) is a progressive disease and major cause of severe visual loss. Toward the discovery of tools for early identification of AMD susceptibility, we evaluated the combined predictive capability of proteomic and genomic AMD biomarkers. We quantified plasma carboxyethylpyrrole (CEP) oxidative protein modifications and CEP autoantibodies by ELISA in 916 AMD and 488 control donors.

Mutation screen of the cone-specific gene, CLUL1, in 376 patients with age-related macular degeneration.

Clusterin is a secreted glycoprotein expressed ubiquitously in many tissues that appears to function as a molecular chaperone capable of protecting stressed proteins. It is upregulated in many different forms of neurodegeneration and is thought to represent a defense response against neuronal damage. Clusterin has been found to be a common protein identified in drusen preparations isolated from the retina of donor eyes of patients with age-related macular degeneration (AMD), the leading cause of blindness in the elderly population of developed countries.

Functional characterization of Escherichia coli GlpG and additional rhomboid proteins using an aarA mutant of Providencia stuartii.

The Providencia stuartii AarA protein is a member of the rhomboid family of intramembrane serine proteases and required for the production of an extracellular signaling molecule that regulates cellular functions including peptidoglycan acetylation, methionine transport, and cysteine biosynthesis. Additional aarA-dependent phenotypes include (i) loss of an extracellular yellow pigment, (ii) inability to grow on MacConkey agar, and (iii) abnormal cell division. Since these phenotypes are easily assayed, the P.

Isolation of lacZ fusions to Proteus mirabilis genes regulated by intercellular signaling: potential role for the sugar phosphotransferase (Pts) system in regulation.

Using a mini-Tn5lacZ1 reporter transposon, lacZ fusions have been identified in Proteus mirabilis that are activated by the accumulation of self-produced extracellular signals. Genes identified by this approach include putative homologs of pgm, nlpA and two genes of unknown function. The extracellular signal(s) involved in activation were resistant to the effects of acid and alkali.