|Ph.D Student||Segal Elena|
|Subject||The role of Zinc and Nitric Oxide in Modulation of|
Information Processing in the Distal
|Department||Department of Medicine||Supervisor||Professor Emeritus Ido Perlman|
|Full Thesis text|
Intricate neural interactions between retinal cells transform the simple hyperpolarizing photoresponses of photoreceptors into color-, spatially- and temporally-coded responses of ganglion cells. These interactions undergo dynamic changes to adjust retinal function to changing conditions of illumination. Nitric oxide (NO) was shown to be a background neuromodulator in the retina, and recently, zinc ions were also suggested to modulate retinal function.
NO: The responses to light stimuli of different wavelengths and intensities of C-type horizontal cells (HCs) were recorded, while changing retinal NO level and background illumination. Raising the retinal level of NO, by adding the precursor for its synthesis (L-Arginine), augmented the depolarizing photoresponses, elicited by long-wavelength light stimuli, and reduced the hyperpolarizing photoresponses elicited by short-wavelength light stimuli. Lowering retinal level of NO by adding L-NAME, an inhibitor of NO synthesis, induced the opposite effects. However, the total voltage range of operation remained constant regardless of the NO level. Similar observations were seen during background illumination of different colors. NO did not modulate color opponency. We suggest that NO does not modulate color information processing in the turtle retina.
Zinc: Immersion autometallography indicated an adaptation-dependent distribution of free zinc ions in the turtle retina. At darkness, zinc is abundant in the extracellular space of all retinal layers. After light adaptation, it is concentrated inside the photoreceptors, leaving the inner retina free of zinc.
The photoresponses of L1-type HCs and the electroretinogram (ERG) were recorded, while changing retinal zinc level and background illumination. Raising the retinal level of zinc (adding ZnCl2) reduced the a-, b- and d-waves of the ERG. It also caused a reduction of the large amplitude photoresponses and augmentation of the small amplitude photoresponses of L1-type HCs, thus, improving sensitivity. The effect of zinc upon light responsiveness became more pronounced as the background light was made brighter, but the improvement in sensitivity decreased. Moreover, zinc increased the Vss/Vpeak ratio, thus hampering light adaptation. Reducing the retinal level of zinc, by adding a zinc chelator (L-Histidine), increased the ERG waves and the responses of L1-type HCs, but only slightly affected sensitivity. These effects became smaller as the background light intensity was increased. Our findings suggest that zinc, co-released with glutamate from the photoreceptors terminals in darkness, serves as dark signal, improving retinal cells sensitivity.