Biomedical subjects

Martin L Katz

Publications and source records attributed to Martin L Katz.

At least 19 recordsLinked to original sources

PubMed2006

A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile Dachshund with neuronal ceroid lipofuscinosis.

The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases characterized by progressive neuropathy and the accumulation of autofluorescent cytoplasmic granules. Clinical signs of a new canine NCL began in a 9-month-old male Dachshund with vomiting, mental dullness, and loss of previously learned commands and rapidly progressed to include disorientation, ataxia, visual deficits, generalized myoclonic seizures, and death at 12 months of age. Neurons throughout the CNS contained autofluorescent storage granules that stained with periodic acid-Schiff and Luxol fast blue stains. Electron microscopy revealed that the storage granule contents consisted of curvilinear-appearing material characteristic of human late infantile NCL caused by CLN2 mutations. Nucleotide sequence analysis of canine TPP1, the ortholog of human CLN2, revealed a single nucleotide deletion in exon 4 which predicted a frame shift with a premature stop codon. Brain tissue from the affected dog lacked detectable activity of the tripeptidyl-peptidase enzyme encoded by TPP1, whereas the specific activities of 15 other lysosomal enzymes were higher than those in the brains of three control dogs. The affected Dachshund was homozygous for the mutant c.325delC allele, his sire and dam were heterozygotes, and 181 unrelated dogs, including 77 Dachshunds, were all homozygous for the wild-type allele. A DNA assay that detects the mutant allele will help Dachshund breeders avoid producing affected puppies in future generations. Furthermore, this Dachshund NCL may prove to be a useful model for studying the pathogenesis of neurodegeneration in human late infantile NCL and for evaluating novel therapeutic interventions for this disease.

Aminopeptidases↗

PubMed2006

A mutation in the cathepsin D gene (CTSD) in American Bulldogs with neuronal ceroid lipofuscinosis.

We obtained DNA, brains, and eyes from American Bulldogs with neurodegeneration due to neuronal ceroid lipofuscinosis (NCL). The diagnosis of NCL was confirmed by detection of autofluorescent cytoplasmic inclusions within neurons throughout the brains, in retinal ganglion cells, and along outer limiting membranes of the retinas. Electron microscopy revealed that the inclusions had coarsely granular matrices surrounding well-delineated spherical structures and that the inclusions near the retinal outer limiting membranes were within photoreceptor cells, mostly cones. Affected American Bulldogs were homozygous for the A allele of a G to A transition in the cathepsin D gene (CTSD), which predicts the conversion of methionine-199 to an isoleucine. Only the G allele was detected in DNA samples from 131 randomly selected dogs representing 108 breeds other than American Bulldog; however, the A allele had a frequency of 0.28 among 123 genotyped American Bulldogs. Transmission analysis in a 99 dog pedigree of American Bulldogs indicated a probability of less than 10(-7) that alleles from any mutation unlinked to CTSD would be concordant with the pedigree and phenotypes of the dogs. Brain samples from affected dogs had 36% of the cathepsin D-specific enzymatic activity found in control dog brains; whereas, specific enzymatic activities of 15 other lysosomal enzymes were unchanged or increased. Compared to previously described NCLs in mice and sheep that completely lack cathepsin D activity, the clinical course of NCL in the American Bulldogs was less severe and more closely resembled that of many human NCLs.

Animals↗

PubMed2006

Ocular phenotype in a mouse gene knockout model for infantile neuronal ceroid lipofuscinosis.

Mutations in the human protein palmitoyl thioesterase-1 (PPT-1) gene result in an autosomal recessive neurodegenerative disorder designated neuronal ceroid lipofuscinosis (NCL), type CLN1, or infantile NCL. Among the symptoms of the CLN1 disease are accumulation of autofluorescent lysosomal storage bodies in neurons and other cell types, seizures, motor and cognitive decline, blindness, and premature death. Development of an effective therapy for this disorder will be greatly assisted by the availability of suitable animal models. A mouse PPT-1 gene knockout model has recently been generated. Studies were performed to determine whether the mouse model exhibits ocular features of the human CLN1 disorder. A progressive accumulation of autofluorescent storage material in all layers of the retina was observed in the PPT-1 knockout mice. Accompanying the storage body accumulation was a modest loss of cells with nuclei in the outer and inner nuclear layers. As indicated by electroretinogram (ERG) responses, retinal function was only mildly impaired at 4 months of age but was severely impaired by 8 months, despite only modest changes in retinal morphology. The pupillary light reflex (PLR), on the other hand, was exaggerated in the knockout mice. The apparent anomaly between the ERG and the PLR findings suggests that disease-related PLR changes may be due to changes in extraocular signal processing. The pronounced ocular phenotype in the PPT-1 knockout mice makes these animals a good model for testing therapeutic interventions for treatment of the human CLN1 disorder.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Where have all the antibiotic patents gone?

Patent and regulatory hurdles combined with low returns on investment are stifling antibiotic R&D in the pharmaceutical industry.

Anti-Bacterial Agents↗

PubMed2005

Embryonic stem cell-derived neural progenitors incorporate into degenerating retina and enhance survival of host photoreceptors.

Embryonic stem (ES) cells differentiate into all cell types of the body during development, including those of the central nervous system (CNS). After transplantation, stem cells have the potential to replace host cells lost due to injury or disease or to supply host tissues with therapeutic factors and thus provide a functional benefit. In the current study, we assessed whether mouse neuralized ES cells can incorporate into retinal tissue and prevent retinal degeneration in mnd mice. These mice have an inherited lysosomal storage disease characterized by retinal and CNS degeneration. Sixteen weeks after intravitreal transplantation into adult mice, donor cells had incorporated into most layers of the retina, where they resembled retinal neurons in terms of morphology, location in the retina, and expression of cell type-specific marker proteins. Presence of these donor cells was correlated with a reduction in the sizes and numbers of lysosomal storage bodies in host retinal cells. The presence of transplanted donor cells was also accompanied by enhanced survival of host retinal neurons, particularly photoreceptors. These results demonstrate that neuralized ES cells protect host neurons from degeneration and appear to replace at least some types of lost neurons.

Animals↗

PubMed2005

Behavioral assessment in mouse models of neuronal ceroid lipofuscinosis using a light-cued T-maze.

Learning impairment is a common feature of the neuronal ceroid lipofuscinoses (NCL), a family of lysosomal storage disorders associated with progressive neurodegeneration. Murine models for the neuronal ceroid lipofuscinoses include the well-characterized motor neuron degeneration (mnd/mnd) model for one variant of late infantile NCL (CLN8), and the more recently generated models for the infantile (CLN1) and juvenile (CLN3) forms of NCL. To determine whether these mouse models exhibit behavioral deficits analogous to the learning impairment characteristic of the human disorders, the performance of these animals on an associative learning task was assessed. The abilities of affected and normal control mice to associate a light stimulus with a food reward were evaluated in 14-16-week-old animals using a T-maze. Normal mice were able to reach a criterion for having learned to make the association within a mean of 9.4 trials. The CLN8 and CLN3 mice, on the other hand, required means of 26.2 and 27.5 trials, respectively, to reach the same performance criterion (p<0.05), whereas none of the CLN1 mice were able to reach the criterion within a limit of 30 trials. The poor performance of the mutant mice did not appear to result from impaired retinal function; mice of all three strains exhibited retinal electrophysiological responses to dim light flashes and displayed robust pupillary light reflexes. Associative learning deficits appear to be an early disease phenotype in the NCL mouse models that will be useful for assessing the efficacy of therapeutic interventions such as gene or stem cell therapies.

Analysis of Variance↗

PubMed2005

A mutation in the CLN8 gene in English Setter dogs with neuronal ceroid-lipofuscinosis.

A heritable neurodegenerative disease of English Setters has long been studied as a model of human neuronal ceroid-lipofuscinosis (NCL). Megablast searches of the first build of the canine genome for potential causative genes located the CLN8 gene near the q telomere of canine chromosome 37, close to a marker previously linked to English Setter NCL. Sequence analysis of the coding region from affected dogs revealed a T-to-C transition in the CLN8 gene that predicts a p.L164P missense mutation. Leucine 164 is conserved in four other mammalian species. The C allele co-segregated with the disease phenotype in a two-generation English Setter family in a pattern consistent with autosomal recessive inheritance. All four NCL-affected family members were C/C homozygotes and all four obligate carriers were C/T heterozygotes; whereas, 103 unrelated dogs were all T/T homozygotes. These findings indicate that the CLN8 T-to-C transition is the likely cause of English Setter NCL.

Amino Acid Sequence↗

PubMed2005

Stem cells for retinal degenerative disorders.

Many systemic and eye-specific genetic disorders are accompanied by retinal degenerations that lead to blindness. In some of these diseases retinal degeneration occurs early in life and is quite rapid, whereas in other disorders, retinal degeneration starts later and progresses very slowly. At present, no therapies are available to patients for preventing or reversing the retinal degeneration that occurs in these diseases. Implantation of neural progenitor cells into the eye may be a means by which to retard or even reverse degeneration of the retina. To evaluate the potential of neural precursor cell implantation for treating retinal degenerative disorders, neuralized mouse embryonic stem cells from green fluorescent protein (GFP) transgenic mice were administered intravitreally to normal mice, mice with early retinal degeneration, and mice with slowly progressing retinal degeneration. In normal mice, the donor cells remained in the vitreous cavity and did not associate with the host retina. In mice with early retinal degeneration, implantation of the neural precursors was performed after the degeneration was almost complete. In these animals, the donor cells primarily associated closely with the inner surface of the retina, although a small fraction of donor cells did integrate into the host retina. Donor cells implanted in mice with slowly progressing retinal degeneration also associated with the inner retinal surface, but many more of the cells integrated into the retina. These findings indicate the importance of host tissue-donor cell interactions in determining the fate of implanted neural precursor cells. These interactions will be a major consideration when devising strategies for using cell implantation therapies for neurodegenerative disorders.

Animals↗

PubMed2005

Assessment of retinal function and characterization of lysosomal storage body accumulation in the retinas and brains of Tibetan Terriers with ceroid-lipofuscinosis.

OBJECTIVE: To characterize lysosomal storage body accumulation in the retina and brain of Tibetan Terriers with ceroid-lipofuscinosis and determine whether the disease in these dogs is accompanied by impaired retinal function and retinal degeneration. ANIMALS: Three 7- to 10-year-old Tibetan Terriers with ceroid-lipofuscinosis and 1 healthy 5-year-old Tibetan Terrier. PROCEDURE: Owners completed a questionnaire to identify behavioral and physical signs indicative of ceroid-lipofuscinosis. Neurologic, behavioral, and ophthalmologic evaluations, including full-field electroretinograms, were performed on each dog. Fluorescence, light, and electron microscopy were performed on specimens of retina, cerebral cortex, and cerebellum of all dogs postmortem. RESULTS: Behavioral assessments of the affected dogs revealed moderate visual impairment in low-light conditions but good vision in bright light. On funduscopic evaluation of these dogs, abnormalities detected ranged from none to signs of moderately advanced retinal degeneration. Compared with findings in the control dog, electroretinography revealed depressed rod cell function with some impairment of cone cell function in the affected dogs. Morphologically, disease-specific storage bodies were detected in retinal Müller cells and neurons, particularly in ganglion cells, and in cells of the cerebral cortex and cerebellum in affected dogs. Substantial photoreceptor cell loss and disruption of photoreceptor outer segment morphology appeared to develop late in the disease. IMPLICATIONS FOR HUMAN MEDICINE: The similarities between ceroid-lipofuscinosis in Tibetan Terriers and some forms of ceroid-lipofuscinosis in humans suggest that the canine disease may have a genetic and biochemical basis similar to that of one of the ceroid-lipofuscinosis disorders in humans.

Adaptation, Ocular↗

PubMed2004

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. Substantial evidence indicates that Vitamin A derivatives (retinoids) are required for RPE lipofuscin formation. The RPE and adjacent retina contain retinoids in the forms of retinol, retinyl esters, and retinaldehyde. Previous research has demonstrated that retinaldehydes are directly involved in the formation of one RPE lipofuscin fluorophore. However, RPE lipofuscin contains many other fluorophores. It has not been determined which retinoids are involved in the formation of these fluorescent compounds. Mice with a mutation in the Rpe65 gene contain substantial levels of retinol and retinyl esters in the RPE, but little if any retinaldehydes in either the RPE or retina. Therefore, these mice could be used to determine whether retinaldehydes are required for formation of all of the RPE lipofuscin fluorophores. Normal mice were given intraocular injections of a protease inhibitor, which resulted in the rapid accumulation in the RPE of lipofuscin-like inclusions. These inclusions exhibited fluorescence properties typical of RPE lipofuscin. Rpe65-/- mice treated with the protease inhibitor also accumulated inclusions similar to those observed in the normal mice. However, these inclusions did not fluoresce under the conditions used to visualize lipofuscin fluorescence. These findings indicate that the aldehyde form of Vitamin A is required for the formation of not only one, but all of the RPE lipofuscin fluorophores.

Aging↗

PubMed2004

Neural differentiation of mouse embryonic stem cells in vitro and after transplantation into eyes of mutant mice with rapid retinal degeneration.

Embryonic stem (ES) cells can differentiate into many specialized cell types, including those of the nervous system. We evaluated the differentiation of enhanced green fluorescent protein (EGFP)-expressing B5 mouse ES cells in vitro and in vivo after transplantation into the eyes of mice with hereditary retinal degeneration. After neural induction with retinoic acid, the majority of cells in embryoid bodies expressed markers for neural progenitors as well as for immature and mature neurons and glial cells. When induced ES cells were plated in vitro, further differentiation was observed and the majority of cells expressed beta-III Tubulin, a marker for immature neurons. In addition, many plated cells expressed markers for mature neurons or glial cells. Four days after intravitreal transplantation into the eyes of rd1 mice (a model of rapid retinal degeneration), donor cells appeared attached to the vitreal surface of the retina. After 6 weeks in vivo, most transplanted cells remained adherent to the inner retinal surface, and some donor cells had integrated into the retina. Transplanted cells exhibited some properties typical of neurons, including extensive process outgrowth with numerous varicosities and expression of neuronal and synaptic markers. Therefore, after induction B5 ES cells can acquire the morphologies of neural cells and display markers for neuronal and glial cells in vitro and in vivo. Furthermore, when placed in the proper microenvironment ES-derived neural precursors can associate closely with or migrate into nervous tissue where differentiation appears to be determined by cues provided by the local environment, in this case the degenerating neural retina.

Animals↗

PubMed2003

Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog.

PURPOSE: To assess the efficacy of AAV-mediated gene therapy to restore vision in a large number of RPE65(-/-) dogs and to determine whether systemic and local side effects are caused by the treatment. METHODS: Normal RPE65 dog cDNA was subcloned into an rAAV vector under control of a cytomegalovirus promoter, and an AAV.GFP control vector was also produced with the titers 2 x 10(12) particles/mL and 2 x 10(10) transducing U/mL, respectively. RPE65(-/-) dogs, aged 4 to 30 months were treated with subretinal injections of the AAV.RPE65 and control vectors, respectively, in each eye, and three 24- to 30-month-old normal control dogs with the latter. Baseline and postoperative systemic and ophthalmic examinations, blood screenings, vision testing, and electroretinography (ERG) were performed. Two RPE65(-/-) dogs were killed at 3 and 6 months after treatment for morphologic examination of the retinas. RESULTS: RPE65(-/-) dogs were practically blind from birth with nonrecordable or low-amplitude ERGs. Construct injections or sham surgeries were performed in 28 eyes; 11 were injected subretinally with the AAV.RPE65 construct. ERGs at 3 months after surgery showed that in the latter eyes, dark-adapted b-wave amplitudes recovered to an average of 28% of normal, and light adapted b-wave amplitudes to 32% of normal. ERG amplitudes were not reduced during a 6- to 9-month follow-up. No systemic side effects were observed, but uveitis developed in nine AAV.RPE65-treated eyes. No uveitis was observed in the eyes treated with the control vector. Immunocytochemistry showed expression of RPE65 in the retinal pigment epithelium (RPE) of AAV.RPE65-treated eyes. Fluorescence microscopy showed expression of green fluorescent protein (GFP) in the RPE and, to a lesser extent, in the neural retinas of AAV.GFP-treated eyes. Ultrastructurally, a reversal of RPE lipid droplet accumulation was observed at the AAV.RPE65 transgene injection site, but not at the site of injection of the control vector. CONCLUSIONS: In 10 of 11 treated RPE65(-/-) eyes, gene transfer resulted in development of vision, both subjectively apparent by loss of nystagmus, and objectively recorded by ERG. Structurally, there was reversal of lipid droplet accumulation in the RPE. Uveitis developed in 75% of the transgene-treated eyes, a complication possibly due to an immunopathogenic response to the RPE65 molecule.

Animals↗

PubMed2002

Bernard Strehler-inspiration for basic research into the mechanisms of aging.

Bernard Strehler, who passed away recently, has provided inspiration and intellectual guidance for a generation of scientists interested in the biology of aging. My own career in this field was launched in large part by the ideas and concepts discussed by Dr Strehler in his book, Time, Cells, and Aging. Much of my scientific career has been devoted to studying one aspect of the aging process-the intracellular accumulation of autofluorescent lysosomal storage bodies (lipofuscin) during senescence. Work in my laboratory has contributed to the elucidation of the molecular mechanisms that underlie formation of lipofuscin in the retinal pigment epithelium of the eye. The challenge for the work on lipofuscin, and for much of the current research on aging, is to determine whether specific age-related changes such as lipofuscin accumulation, are involved in determining maximum life span. Bernard Strehler's eloquent statement of this challenge will hopefully continue to inspire new research to further our understanding of the aging phenomenon.

Aging↗

PubMed2002

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. Blood samples were analyzed for plasma-free carnitine and acyl-carnitines concentrations. RESULTS: Neither the mean plasma total carnitine concentration nor the mean fraction of carnitine in the free form differed significantly between Tibetan Terriers with CL and healthy Tibetan Terriers. Among Tibetan Terriers and the general dog population, plasma carnitine concentration increased with age. Castrated males had an overall increase in plasma carnitine concentrations and variability, compared with sexually intact males. By comparison, plasma carnitine concentrations were not significantly different between spayed and sexually intact females. The mean plasma carnitine concentration in the Tibetan Terriers was approximately 22% higher than in the general population of healthy dogs of other breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Contrary to what is seen in early onset CL in English Setters and in humans with some forms of CL, plasma carnitine concentrations are not decreased in the late-onset disorder in Tibetan Terriers. Our large-scale study establishes reference range values for plasma carnitine concentrations in dogs as functions of age and sex that will be useful in evaluating potential carnitine deficiencies in other disorders in dogs.

Age Factors↗

PubMed2002

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. Cell density in the retinal capillaries was evaluated by use of elastase digestion isolation of the retinal vascular bed, and retinal capillary basement membrane thickness was determined by use of electron microscopic analyses. RESULTS: Diabetic pigs fed a normal diet had significantly (P < 0.001) thicker retinal capillary basement membranes than did nondiabetic animals. High fat intake did not contribute to basement membrane thickening. Significant effects of diabetes or diet on retinal capillary cell densities were not observed, nor did diabetes induce formation of microaneurysms typical of advanced diabetic retinopathy. CONCLUSIONS: The rapid development of retinal capillary basement membrane thickening in diabetic pigs makes this animal model useful for early intervention and mechanistic studies for this diabetes-associated microvascular change.

Animals↗

PubMedDate not supplied

What is lipofuscin? Defining characteristics and differentiation from other autofluorescent lysosomal storage bodies.

Lipofuscins, also known as age-pigments, have three defining characteristics: (1) they consist of intracellular secondary lysosomes; (2) they have a yellow autofluorescent emission when excited by near ultraviolet or blue light; and (3) they accumulate during normal senescence. Lysosomal storage bodies with similar fluorescence properties accumulate in various cell types as a result of specific pathological conditions or experimental manipulations. As a class, the latter are often referred to as ceroid pigments. In general, the mechanisms involved in the formation of ceroid pigments cannot be assumed to be closely similar to those involved in lipofuscin formation. In fact, the mechanisms of formation almost certainly differ, not only between lipofuscins and ceroids, but also among different lipofuscins and different ceroids. Presently, the most detailed knowledge about the mechanisms involved in lipofuscin formation come from studies on the retinal pigment epithelium (RPE) of the eye. These studies indicate that at least the autofluorescent constituents of RPE lipofuscin are generated from derivatives of vitamin A that occur in the retina. Oxidative stress to the retina appears to promote the formation of these RPE fluorophores. Whether similar mechanisms are involved in the formation of the lipofuscins that occur in other tissues remains to be determined. The mechanisms involved in RPE lipofuscin fluorophore formation are closely related to metabolic pathways that are specific to the retina. Thus, it appears likely that the mechanisms by which lipofuscins form in other tissues differ fundamentally from those that underlie RPE lipofuscin formation.

Journal Article↗

PubMedDate not supplied

Potential reversibility of lipofuscin accumulation.

It is well established that the lipofuscin content of many post-mitotic cell types increases progressively during normal senescence. This age-related accumulation of lipofuscin may occur either: (1) because lipofuscin, once formed, is never degraded or eliminated from cells; or (2) because, despite turnover of this pigment, the rate of lipofuscin formation exceeds the rate at which it is eliminated. Little research has been performed to distinguish between these possibilities. Several studies suggest that lipofuscin may be turned over. However, definitive demonstrations that such turnover does occur under normal circumstances are lacking. It is possible to specifically halt new lipofuscin formation in the retinal pigment epithelium (RPE) of animals at an age when significant amounts of lipofuscin have accumulated in these cells. By monitoring the RPE for possible decreases in lipofuscin content after new pigment formation has been halted, it should be possible to determine whether previously formed lipofuscin can be eliminated from the RPE.

Journal Article↗

PubMedDate not supplied

Potential role of retinal pigment epithelial lipofuscin accumulation in age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of severe visual impairment in developed countries. The vision loss associated with AMD is the result of degenerative changes in the central region of the retina called the macula. Maintenance of normal structure and function of the macular retina, and of the remainder of the retina as well, is critically dependent on the supporting role of the adjacent retinal pigment epithelium (RPE). Impairment of normal RPE functions is known to result in retinal degeneration and loss of visual function. Thus, it has been hypothesized that the retinal degeneration that characterizes AMD is secondary to age-related deterioration in RPE support functions. Like many other postmitotic cell types, the RPE accumulates autofluorescent lysosomal storage bodies (lipofuscin) during senescence. In human eyes, lipofuscin comes to occupy a substantial fraction of the RPE cytoplasmic volume in the elderly. Does this lipofuscin accumulation contribute to the development of AMD? This question is a specific case of the broader question of whether lipofuscin accumulation in general is detrimental to cells. Unfortunately, definitive data do not exist to allow these questions to be answered. Although a correlation between RPE lipofuscin content and AMD has been reported, a cause-and-effect relationship between RPE lipofuscin accumulation and the development of this disease has not been established. It has been reported that a mutation in a gene encoding a photoreceptor-specific protein results in massive RPE lipofuscin accumulation and early-onset macular degeneration. However, again the accelerated RPE lipofuscin accumulation has not been shown to be the cause of the accompanying macular degeneration. The lack of a definitive link between RPE lipofuscin accumulation and AMD illustrates one of the biggest challenges remaining in lipofuscin research-determining whether lipofuscin accumulation per se has an impact on cell function.

Journal Article↗