טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentVainer Evgrafov Elit
SubjectFunctional Plasticity in the Distal Turtle Retina: The
Interplay between Retinoic Acid, Nitric Oxide and
Dopamine
DepartmentDepartment of Medicine
Supervisor Professor Emeritus Ido Perlman
Full Thesis textFull thesis text - English Version


Abstract

Dopamine, nitric oxide and retinoic acid have all been proposed to act as neuromodulators adjusting visual information processing in the vertebrate retina to varying conditions of ambient illumination. The present study was designed to discover the interactions between these chemicals in affecting distal retinal function in turtle, and to reveal their specific roles in light adaptation.

The effects of dopamine and nitric oxide have been previously studied in the turtle retina. The effects of retinoic have not been tested in turtle, and studying them was the first aim of our research.

Retinoic acid was found to affect the responsiveness to light of cones, horizontal cells and bipolar cells in an intensity-dependent manner. The responses to bright-light stimuli were reduced considerably; while these elicited by dim stimuli were basically unchanged in cones and bipolar cells, and were augmented in horizontal cells. This was reflected in a retinoic acid-induced augmentation of non-linearity of the transfer function between cones and horizontal cells, increasing gain for the smaller cone photoresponses. Overall, retinoic acid was shown to act as a light-adaptive neuromodulator in the distal turtle retina, acting to reduce the desensitizing impact of background illumination upon the retinal network.

In order to achieve our primary goal, we tested the effects of different combinations of retinoic acid, nitric oxide-related drugs and dopamine-related substances in the experimental model.

In previous studies, L-arginine (precursor for nitric oxide synthesis) augmented, while L-NAME (an inhibitor of nitric oxide synthesis) reduced the responsiveness to light of cones, horizontal cells and bipolar cells. Here, co-application of retinoic acid and L-arginine suppressed the responses to a greater extent than did retinoic acid alone. Co-application of retinoic acid and L-NAME produced lesser response suppression than retinoic acid alone. The separate and combined effects of these substances were unaffected by the dopaminergic system.

Independently of dopamine, retinoic acid and nitric oxide increased horizontal cell sensitivity, through apparently distinct mechanisms.

Nitric oxide and background light both produced linearization of the synaptic transfer function between cones and horizontal cells, but the synaptic gain was higher in the background light. Raising nitric oxide and retinoic acid in the dark induced both linearization of the function and an increase in gain, independently of the dopaminergic system.