Ripps Harris

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Ripps
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  • Article
    Destructive changes in the neuronal structure of the FVB/N mouse retina
    (Public Library of Science, 2015-06-19) Yang, Jinnan ; Nan, ChangLong ; Ripps, Harris ; Shen, Wen
    We applied a series of selective antibodies for labeling the various cell types in the mammalian retina. These were used to identify the progressive loss of neurons in the FVB/N mouse, a model of early onset retinal degeneration produced by a mutation in the pde6b gene. The immunocytochemical studies, together with electroretinogram (ERG) recordings, enabled us to examine the time course of the degenerative changes that extended from the photoreceptors to the ganglion cells at the proximal end of the retina. Our study indicates that photoreceptors in FVB/N undergo a rapid degeneration within three postnatal weeks, and that there is a concomitant loss of retinal neurons in the inner nuclear layer. Although the loss of rods was detected at an earlier age during which time M- and S-opsin molecules were translocated to the cone nuclei; by 6 months all cones had also degenerated. Neuronal remodeling was also seen in the second-order neurons with horizontal cells sprouting processes proximally and dendritic retraction in rod-driven bipolar cells. Interestingly, the morphology of cone-driven bipolar cells were affected less by the disease process. The cellular structure of inner retinal neurons, i.e., ChAT amacrine cells, ganglion cells, and melanopsin-positive ganglion cells did not exhibit any gross changes of cell densities and appeared to be relatively unaffected by the massive photoreceptor degeneration in the distal retina. However, Muller cell processes began to express GFAP at their endfeet at p14, and it climbed progressively to the cell’s distal ends by 6 months. Our study indicates that FVB/N mouse provides a useful model with which to assess possible intervention strategies to arrest photoreceptor death in related diseases.
  • Preprint
    Characteristics of period doubling in the rat cone flicker ERG
    ( 2009-10) Shah, Manthan R. ; Alexander, Kenneth R. ; Ripps, Harris ; Qian, Haohua
    When the eye is stimulated by a flickering light, the electroretinogram (ERG) and other electrophysiological responses in the visual pathway often exhibit period doubling. This phenomenon is manifested as an alternation in the shape of the response waveform from cycle to cycle, and also as spectral components at the half-fundamental frequency (F/2) and its odd multiples. Although period doubling has been described in humans as well as in other animals, its features in the rodent flicker ERG have not been characterized. We investigated the properties of period doubling in the rat cone flicker ERG elicited with full field, sinusoidal photic stimuli. Period doubling was observed when the temporal frequency of the stimulus was in the range of 20 to 30 Hz. The F/2 component of the Fourier spectrum of the ERG was more pronounced than its odd harmonics. The magnitude of the cycle-to-cycle variation in amplitude differed depending on whether measurements were based on peak-to-trough or trough-to-peak amplitudes, owing to the relative phase relationship between F/2 and F as a function of stimulus frequency. The frequency-response characteristics of period doubling varied with stimulus contrast, such that reducing the contrast shifted the peak F/2 amplitude to a lower stimulus frequency. Period doubling was evident in rat eyes in which PDA was administered intravitreally, indicating that the phenomenon can occur independently of OFF-pathway activity in the rat retina. The period doubling properties we observed in the flicker ERG response of the rat cone system provide constraints on the nature of the nonlinear feedback mechanism presumed to underlie the period doubling phenomenon.
  • Article
    Review : Taurine : a “very essential” amino acid
    (Emory Eye Center, Zhongshan Ophthalmic Center, Georgia Knights Templar Educational Foundation, and Emory University, 2012-11-12) Ripps, Harris ; Shen, Wen
    Taurine is an organic osmolyte involved in cell volume regulation, and provides a substrate for the formation of bile salts. It plays a role in the modulation of intracellular free calcium concentration, and although it is one of the few amino acids not incorporated into proteins, taurine is one of the most abundant amino acids in the brain, retina, muscle tissue, and organs throughout the body. Taurine serves a wide variety of functions in the central nervous system, from development to cytoprotection, and taurine deficiency is associated with cardiomyopathy, renal dysfunction, developmental abnormalities, and severe damage to retinal neurons. All ocular tissues contain taurine, and quantitative analysis of ocular tissue extracts of the rat eye revealed that taurine was the most abundant amino acid in the retina, vitreous, lens, cornea, iris, and ciliary body. In the retina, taurine is critical for photoreceptor development and acts as a cytoprotectant against stress-related neuronal damage and other pathological conditions. Despite its many functional properties, however, the cellular and biochemical mechanisms mediating the actions of taurine are not fully known. Nevertheless, considering its broad distribution, its many cytoprotective attributes, and its functional significance in cell development, nutrition, and survival, taurine is undoubtedly one of the most essential substances in the body. Interestingly, taurine satisfies many of the criteria considered essential for inclusion in the inventory of neurotransmitters, but evidence of a taurine-specific receptor has yet to be identified in the vertebrate nervous system. In this report, we present a broad overview of the functional properties of taurine, some of the consequences of taurine deficiency, and the results of studies in animal models suggesting that taurine may play a therapeutic role in the management of epilepsy and diabetes.
  • Preprint
    Glycinergic feedback enhances synaptic gain in the distal retina
    ( 2013-09) Jiang, Zheng ; Yang, Jinnan ; Purpura, Lauren A. ; Liu, Yufei ; Ripps, Harris ; Shen, Wen
    Glycine input originates with interplexiform cells, a group of neurons situated within the inner retina that transmit signals centrifugally to the distal retina. The effect on visual function of this novel mechanism is largely unknown. Using gramicidin-perforated patch whole-cell recordings, intracellular recordings, and specific antibody labeling techniques, we examined the effects of the synaptic connections between glycinergic interplexiform cells, photoreceptors, and bipolar cells. To confirm that interplexiform cells make centrifugal feedback on bipolar cell dendrites, we recorded the post-synaptic glycine currents from axon-detached bipolar cells while stimulating pre-synaptic interplexiform cells. The results show that glycinergic interplexiform cells activate bipolar cell dendrites that express the α3 subunit of the glycine receptor, as well as a subclass of unidentified receptors on photoreceptors. By virtue of their synaptic contacts, glycine centrifugal feedback increases glutamate release from photoreceptors, and suppresses the uptake of glutamate by the EAAT2 transporter on photoreceptors. The net effect is a significant increase in the synaptic gain between photoreceptors and their second-order neurons.
  • Article
    Potassium currents distinguish the two subtypes of morphologically distinct skate bipolar cells
    (Marine Biological Laboratory, 2004-12) Qian, Haohua ; Chappell, Richard L. ; Redenti, Stephen ; Ripps, Harris
    Bipolar cells in the vertebrate retina are second-order neurons that convey visual information from photoreceptors to ganglion cells, the neurons that relay the message to the brain. Bipolar cells consist typically of multiple subtypes that differ in their morphology, synaptic connections, and response properties. The individual subtypes are thought to carry different aspects of the visual signal through the retina, and they often exhibit unique membrane properties and neurotransmitter receptors. In the all-rod skate retina, only two morphologically and pharmacologically distinct subtypes of bipolar cell have been identified thus far. The large-field bipolar cells, with extensive dendritic arbors, are glycine-insensitive, whereas the small-field bipolar cells, which have only one or two dendritic branches, are sensitive to glycine. In the present study, we explored further the membrane properties of these two subtypes of skate bipolar cell with emphasis on the voltage-sensitive potassium currents. Our results show that the cells exhibit different voltage-activated current profiles, suggesting that the signals they transmit contain different features of the visual scene.
  • Article
    Histidine suppresses zinc modulation of connexin hemichannels
    (Marine Biological Laboratory, 2004-12) Chappell, Richard L. ; Qian, Haohua ; Zakevicius, Jane ; Ripps, Harris
    Zinc has been shown to modulate hemichannel currents of connexins Cx35 and Cx38 in Xenopus oocytes. In both cases the effects were biphasic; i.e., low concentrations of zinc enhanced, whereas higher concentrations decreased, the magnitudes of the voltage-activated hemichannel currents. The present study was designed to determine the effects of zinc on hemichannels formed by Cx26, a connexin reportedly expressed on dendrites of carp horizontal cells and implicated in a mechanism for photoreceptor feedback. In addition, we examined whether histidine, a zinc chelator, would block the action of zinc on Cx26 hemichannel currents, or would exert a direct effect on those currents.
  • Article
    Neurovascular interaction and the pathophysiology of diabetic retinopathy
    (Hindawi Publishing, 2011) Qian, Haohua ; Ripps, Harris
    Diabetic retinopathy (DR) is the most severe of the several ocular complications of diabetes, and in the United States it is the leading cause of blindness among adults 20 to 74 years of age. Despite recent advances in our understanding of the pathogenesis of DR, there is a pressing need to develop novel therapeutic treatments that are both safe and efficacious. In the present paper, we identify a key mechanism involved in the development of the disease, namely, the interaction between neuronal and vascular activities. Numerous pathological conditions in the CNS have been linked to abnormalities in the relationship between these systems. We suggest that a similar situation arises in the diabetic retina, and we propose a logical strategy aimed at therapeutic intervention.
  • Article
    Review : Zinc’s functional significance in the vertebrate retina
    (Molecular Vision, 2014-07-31) Ripps, Harris ; Chappell, Richard L.
    This review covers a broad range of topics related to the actions of zinc on the cells of the vertebrate retina. Much of this review relies on studies in which zinc was applied exogenously, and therefore the results, albeit highly suggestive, lack physiologic significance. This view stems from the fact that the concentrations of zinc used in these studies may not be encountered under the normal circumstances of life. This caveat is due to the lack of a zinc-specific probe with which to measure the concentrations of Zn2+ that may be released from neurons or act upon them. However, a great deal of relevant information has been garnered from studies in which Zn2+ was chelated, and the effects of its removal compared with findings obtained in its presence. For a more complete discussion of the consequences of depletion or excess in the body’s trace elements, the reader is referred to a recent review by Ugarte et al. in which they provide a detailed account of the interactions, toxicity, and metabolic activity of the essential trace elements iron, zinc, and copper in retinal physiology and disease. In addition, Smart et al. have published a splendid review on the modulation by zinc of inhibitory and excitatory amino acid receptor ion channels.
  • Article
    Harmonic analysis of the cone flicker ERG of rabbit
    (Elsevier B.V., 2010-10-23) Qian, Haohua ; Alexander, Kenneth R. ; Ripps, Harris
    Harmonic analysis was used to characterize the rabbit flicker ERG elicited by sinusoidally modulated full-field stimuli under light-adapted conditions. The frequency-response function for fundamental amplitude, derived from Fourier analysis of the ERG waveforms, exhibited two limbs, with an amplitude minimum at approximately 30 Hz, and a high-frequency region peaking at around 45 Hz and extending to more than 100 Hz at higher adapting levels. At low frequencies (<20 Hz), the fundamental response amplitude was independent of mean luminance (Weber law behavior), whereas the response amplitude at high stimulus frequencies varied nonlinearly with mean luminance. At low frequencies, intravitreal administration of L-AP4, which blocks ON-pathway activity, reduced the fundamental response amplitude and produced a phase shift. On the other hand, PDA, which reduces OFF-pathway activity, had a minimal effect on both the response amplitude and phase at low frequencies. At high frequencies, L-AP4 increased the fundamental response amplitude at low mean luminances, whereas PDA had only a small effect on amplitude and phase. Both pharmacologic agents removed the minimum in the amplitude-frequency function as well as the abrupt change in phase at stimulus frequencies near 30 Hz. The results suggest that there is a nonlinear interaction between ON- and OFF-pathway activity over the entire stimulus frequency range examined in this study. These findings provide a basis for formulating protocols to evaluate the effect of pharmacologic agents and/or disease on the cone flicker ERG of rabbit.