Age-related macular degeneration (ARMD) is the leading cause of vision loss in developed countries. Hallmarks of the disease are well known; indeed, this pathology is characterized by lipofuscin accumulation, is principally composed of lipid-containing residues of lysosomal digestion. The N-retinyl-N-retinylidene ethanolamine (A2E) retinoid which is thought to be a cytotoxic component for RPE i...

PURPOSE To investigate the effect of ABCA4 mutation status on lipofuscin-related quantitative autofluorescence (qAF) in humans and on bisretinoid accumulation in mice. METHODS Genotyped parents (n = 26; age 37-64 years) of patients with biallelic ABCA4-related retinopathy underwent in-depth retinal phenotyping including qAF imaging as a surrogate measure for RPE lipofuscin accumulation. In ad...

Many pathologies of the central nervous system (CNS) originate from excess of reactive free radicals, notably reactive oxygen species (ROS), and oxidative stress. A phenomenon which usually runs in parallel with oxidative stress is unsaturated lipid peroxidation, which, via a chain reaction, contributes to the progression of disbalanced redox homeostasis. Among long-chain (LC) polyunsaturated f...

BACKGROUND Pompe disease, an inherited deficiency of lysosomal acid alpha-glucosidase (GAA), is a metabolic myopathy with heterogeneous clinical presentations. Late-onset Pompe disease (LOPD) is a debilitating progressive muscle disorder that can occur anytime from early childhood to late adulthood. Enzyme replacement therapy (ERT) with recombinant human GAA is currently available for Pompe pat...

Ultrastructural study of autoptic cerebral tissue from a patient with hereditary degenerative disease of the nervous system revealed lipofuscin-like bodies and variable sized osmiophilic granular masses in neurons. Autofluorescent granules were also found in neurons. Biochemical study demonstrated a deficiency of diaminobenzidine peroxidase and the accumulation of lipopigment in cerebral tissue.

PURPOSE Age-related macular degeneration (AMD) is accompanied by increased complement activation, and by lipofuscin accumulation in retinal pigment epithelial (RPE) cells due to incomplete degradation of photoreceptor outer segments (POS). The influence of POS, ultraviolet (UV)-irradiated POS and human complement sera (HCS) on cytokine secretion from RPE cells was therefore examined. METHODS ...

Purpose By multimodal imaging, and the use of mouse and in vitro models, we have addressed changes in fundus autofluorescence (488 and 790 nm) and observed interactions between the photooxidative stress imposed by RPE bisretinoid lipofuscin and the oxidative impact of systemic sodium iodate (NaIO3). Methods Abca4-/-, wild-type, and Rpe65rd12 mice were given systemic injections of NaIO3 (30 mg...

The number of nerve cells in the nucleus basalis of Meynert in normally aged persons is reduced by 30% by 90 years of age and cytoplasmic RNA content and nucleolar volume by about 20%. In Alzheimer's disease the changes are greatly exacerbated, with the cell number being depleted by a further 60% and cytoplasmic RNA content and nucleolar volume by an extra 35%. Moreover, younger patients with A...

PURPOSE Studies implicate activation of complement among the processes involved in the pathogenesis of age-related macular degeneration (AMD). Questions pertain to the trigger(s) responsible for the complement-associated events. The authors previously reported that photooxidation products of A2E can activate complement. Here they have further explored these events. METHODS In vitro assays usi...