טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentLevy Hanna
SubjectThe Role of Nitric Oxide in Information Proccessing in the
Distal Retina of the Turtle
DepartmentDepartment of Medicine
Supervisor Professor Emeritus Ido Perlman


Abstract

    Nitric oxide (NO) has been identified to play an important role in inter cellular communication in different tissues. In the retina, numerous cells were found to contain Nitric Oxide Synthase (NOS), the enzyme that synthesizes NO from L-arginine, and its activity was shown to depend upon the state of adaptation.

In this study, we examined the modulatory effect of NO on visual information processing in the distal retina of the turtle. Since NO has been suggested to act as a light-adapting signal, the main interest was given to its effects upon the retina under different adaptation conditions.

In order to achieve these goals the photoresponses of cones and horizontal cells were recorded intracellulary. The electroretinogram (ERG) was recorded to assess the function of ON-center bipolar cells. Light stimuli, of different intensities, were applied in the dark-adapted state and during background illumination of different intensities. In order to identify the contribution of NO to the distal retina, solutions containing the substrate or an inhibitor to NO synthesis or an NO donor were used.

Increase in the retinal concentration of NO caused augmentation of light responsiveness of cones, horizontal cells and ON-center bipolar cells. Inhibition of NO synthesis reduced light responsiveness of cones and ON-center bipolar cells while horizontal cells exhibited a dose depended effect. The reduction in the photoresponses caused by NO inhibitor indicates that NO is released endogenously in the retina.  Experiments that were performed during background illumination showed that increase in NO concentration in the retina produced an augmentation of the photoresponses - though to a smaller degree then the effect that was observed in dark-adapted state. Reducing the retinal concentration of NO by adding an inhibitor to NO synthesis exerted a strong effect also in light-adapted conditions.

Our findings are consistent with the hypothesis that the NO system is involved in information processing in the distal retina of the turtle and that NO acts as a light-adapting signal. The rate of endogenous synthesis of NO depends directly upon the intensity of background illumination. NO seems to act upon guanylate cyclase in the cone outer segments but also in more proximal sites like transmitter release from the cone terminals and the interactions between the cone neurotransmitter and its receptors on the horizontal cell membrane.