Qian Haohua

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Qian
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Haohua
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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.

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Article

Neurovascular interaction and the pathophysiology of diabetic retinopathy

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.

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Article

Potassium currents distinguish the two subtypes of morphologically distinct skate bipolar cells

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.

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Article

Harmonic analysis of the cone flicker ERG of rabbit

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.

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Article

Histidine suppresses zinc modulation of connexin hemichannels

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.

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