Peter Gouras

Bio: Peter Gouras is an academic researcher from Columbia University. The author has contributed to research in topics: Retina & Retinal pigment epithelium. The author has an hindex of 62, co-authored 198 publications receiving 12059 citations. Previous affiliations of Peter Gouras include National Institutes of Health & Max Planck Society.

Functional properties of ganglion cells of the rhesus monkey retina.

Abstract: Three general classes of cells were identified in a sample of 460 cells recorded from all areas of the retina subserving the central 40 degrees of vision in the rhesus monkey. 2. One class (colour-opponent) had sustained colour-opponent responses and concentrically organized receptive fields, in which usually one cone mechanism mediated the centre response and one or two different cone mechanisms mediated the antagonistic surround. A few cells of this class had non-concentric (co-extensive) receptive field organization. 3. A second class (broad-band) had transient responses and concentrically organized receptive fields, in which usually two cone mechanisms mediated the centre response. In most cells, the surround had the same spectral sensitivity as the centre and the cells had non-colour opponent responses. In other cells, the surround had a spectral sensitivity different to that of the centre and the cells had colour-opponent responses. 4. The third class (non-concentric) did not have concentrically organized receptive fields. One group of cells had extremely phasic on-, off- or on-off responses and no spontaneous activity, another group had characteristically regular spontaneous activity and was responsive only to moving stimuli. 5. Cells of the colour-opponent class with concentric receptive fields had the smallest centre-sizes, which did not vary markedly from cell to cell (mean 15 mum); cells of the non-concentric class with phasic responses had the largest centre-sizes, which varied from cell to cell. 6. Colour-opponent cells comprised the highest proportion of cells near the foveola; broad-band cells comprised the highest proportion in the more peripheral areas of the retina; non-concentric cells were equally represented in all areas.

Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein

Abstract: Retinol-binding protein (RBP) is the sole specific transport protein for retinol (vitamin A) in the circulation, and its single known function is to deliver retinol to tissues Within tissues, retinol is activated to retinoic acid, which binds to nuclear receptors to regulate transcription of >300 diverse target genes In the eye, retinol is also activated to 11-cis-retinal, the visual chromophore We generated RBP knockout mice (RBP(-/-)) by gene targeting These mice have several phenotypes Although viable and fertile, they have reduced blood retinol levels and markedly impaired retinal function during the first months of life The impairment is not due to developmental retinal defect Given a vitamin A-sufficient diet, the RBP(-/-) mice acquire normal vision by 5 months of age even though blood retinol levels remain low Deprived of dietary vitamin A, vision remains abnormal and blood retinol declines to undetectable levels Another striking phenotype of the mutant mice is their abnormal retinol metabolism The RBP(-/-) mice can acquire hepatic retinol stores, but these cannot be mobilized Thus, their vitamin A status is extremely tenuous and dependent on a regular vitamin A intake Unlike wild-type mice, serum retinol levels in adult RBP(-/-) animals become undetectable after only a week on a vitamin A-deficient diet and their retinal function rapidly deteriorates Thus RBP is needed for normal vision in young animals and for retinol mobilization in times of insufficient dietary intake, but is otherwise dispensable for the delivery of retinol to tissues

Rhodopsin mutations in autosomal dominant retinitis pigmentosa.

Abstract: DNA samples from 161 unrelated patients with autosomal dominant retinitis pigmentosa were screened for point mutations in the rhodopsin gene by using the polymerase chain reaction and denaturing gradient gel electrophoresis. Thirty-nine patients were found to carry 1 of 13 different point mutations at 12 amino acid positions. The presence or absence of the mutations correlated with the presence or absence of retinitis pigmentosa in 174 out of 179 individuals tested in 17 families. The mutations were absent from 118 control subjects with normal vision.

Identification of cone mechanisms in monkey ganglion cells

Abstract: 1. Blue, green, and red sensitive cone mechanisms have been studied in two types of on-centre ganglion cells in the Rhesus monkey's retina. 2. One type of cell receives signals from both green and red sensitive cone mechanisms, both of which excite in the centre and inhibit in the periphery of the cell's receptive field. These cells discharge transiently to maintained stimuli of any wave-length and are called phasic. 3. The second type of cell receives excitatory signals from only one cone mechanism, either blue, green or red sensitive, in the centre, and inhibition from another cone mechanism in the periphery of its receptive field. These cells discharge continuously to maintained stimuli of appropriate wave-length and are called tonic. 4. Tonic cells outnumber phasic cells although both are found adjacent to one another throughout the retina. Phasic cells are relatively more common toward the periphery and tonic cells relatively more common toward the fovea.

Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy

Abstract: Mutations in the beta subunit of the cGMP phosphodiesterase gene (beta PDE) can cause a recessively inherited retinal degeneration in several species, including mice, dogs and humans. We tested the possibility of altering the course of retinal degeneration in the rd mouse through subretinal injection of a recombinant replication-defective adenovirus that contains the murine cDNA for wild-type (beta PDE, Ad.CMV beta PDE. Subretinal injection of Ad.CMV beta PDE results in beta PDE transcripts and increased PDE activity and delays photoreceptor cell death by six weeks. The findings demonstrate cell rescue by in vivo gene transfer, thus supporting the feasibility of treating an inherited retinal degeneration by somatic gene therapy.

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Adipokines in inflammation and metabolic disease

Abstract: The worldwide epidemic of obesity has brought considerable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function.

Segregation of form, color, movement, and depth: anatomy, physiology, and perception

Abstract: Anatomical and physiological observations in monkeys indicate that the primate visual system consists of several separate and independent subdivisions that analyze different aspects of the same retinal image: cells in cortical visual areas 1 and 2 and higher visual areas are segregated into three interdigitating subdivisions that differ in their selectivity for color, stereopsis, movement, and orientation. The pathways selective for form and color seem to be derived mainly from the parvocellular geniculate subdivisions, the depth- and movement-selective components from the magnocellular. At lower levels, in the retina and in the geniculate, cells in these two subdivisions differ in their color selectivity, contrast sensitivity, temporal properties, and spatial resolution. These major differences in the properties of cells at lower levels in each of the subdivisions led to the prediction that different visual functions, such as color, depth, movement, and form perception, should exhibit corresponding differences. Human perceptual experiments are remarkably consistent with these predictions. Moreover, perceptual experiments can be designed to ask which subdivisions of the system are responsible for particular visual abilities, such as figure/ground discrimination or perception of depth from perspective or relative movement--functions that might be difficult to deduce from single-cell response properties.

The Retinal Pigment Epithelium in Visual Function

Abstract: Located between vessels of the choriocapillaris and light-sensitive outer segments of the photoreceptors, the retinal pigment epithelium (RPE) closely interacts with photoreceptors in the maintenance of visual function. Increasing knowledge of the multiple functions performed by the RPE improved the understanding of many diseases leading to blindness. This review summarizes the current knowledge of RPE functions and describes how failure of these functions causes loss of visual function. Mutations in genes that are expressed in the RPE can lead to photoreceptor degeneration. On the other hand, mutations in genes expressed in photoreceptors can lead to degenerations of the RPE. Thus both tissues can be regarded as a functional unit where both interacting partners depend on each other.

Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes

Abstract: In obesity and type 2 diabetes, expression of the GLUT4 glucose transporter is decreased selectively in adipocytes. Adipose-specific Glut4 (also known as Slc2a4) knockout (adipose-Glut4-/-) mice show insulin resistance secondarily in muscle and liver. Here we show, using DNA arrays, that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4-/- mice. We show that serum RBP4 levels are elevated in insulin-resistant mice and humans with obesity and type 2 diabetes. RBP4 levels are normalized by rosiglitazone, an insulin-sensitizing drug. Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of Rbp4 enhances insulin sensitivity. Fenretinide, a synthetic retinoid that increases urinary excretion of RBP4, normalizes serum RBP4 levels and improves insulin resistance and glucose intolerance in mice with obesity induced by a high-fat diet. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and impairs insulin signalling in muscle. Thus, RBP4 is an adipocyte-derived 'signal' that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes.