The doctoral dissertations of the former Helsinki University of Technology (TKK) and Aalto University Schools of Technology (CHEM, ELEC, ENG, SCI) published in electronic format are available in the electronic publications archive of Aalto University - Aaltodoc.
Aalto

Phototransduction in Retinal Rods and Cones: Effects of Temperature and Background Light, and an Application for Testing Drug Delivery

Soile Nymark

Dissertation for the degree of Doctor of Science in Technology to be presented with due permission of the Faculty of Information and Natural Sciences for public examination and debate in Auditorium D at Helsinki University of Technology (Espoo, Finland) on the 6th of June, 2009, at 12 noon.

Overview in PDF format (ISBN 978-951-22-9928-7)   [1151 KB]
Dissertation is also available in print (ISBN 978-951-22-9927-0)

Abstract

The photoreceptor cells of the vertebrate retina share a common morphological design and molecular scheme for phototransduction. Within this framework, there are great functional differences with respect to response amplification, kinetics, and adaptability to different mean light levels, first, between the two main classes of photoreceptors, rods and cones, and second, between different taxonomic groups. The present thesis analyses functional differences and similarities between i) mammalian and amphibian photoreceptors, and ii) rods and cones by studying effects of temperature on electrophysiological response properties.

The research is based on characterisation of sensitivity and photoresponse kinetics in rods and cones of two mammals (rat and mouse), and two amphibians (frog and toad). Photoresponses to light pulses of incremental strength were recorded by the electroretinogram (ERG) technique across isolated aspartate-treated retinas at different temperatures in the range 2 - 37 °C, and at different levels of mean illumination.

One objective was to investigate how the major functional differences between different vertebrate photoreceptors can be explained without assuming large differences in the properties of the phototransduction molecules. A general conclusion is that at the same temperature photoreceptors of mammals and amphibians exhibit similar functional properties. In rods, the remaining differences in the electrophysiological properties can largely be explained by differences in outer-segment size and morphology. In cones the picture is more complex due to the highly folded structure of the outer segment as well as the presence of thermal isomerizations of visual pigment, which may occur at a rate possibly high enough to 'light-adapt' cones in darkness.

Another objective was to relate the capacity for temporal integration of dark-adapted rod photoreceptors to the integration time of vision and absolute visual sensitivity. A strong correlation was found between temporal integration in rods and in a visually guided behaviour of toads at different temperatures. The results allow the conclusion that temporal integration is mainly set by the rods and explains a considerable part of differences in absolute visual sensitivity between amphibians and mammals.

The thesis also includes a project in which the aim was to develop a method where the vertebrate retina could be used as a biosensor for monitoring controlled drug release from temperature-sensitive polymeric carriers. The developed method enabled accurate concentration determinations of the model drug 3-isobutyl-1-methylxanthine (IBMX) based on the square root dependence of photoresponse kinetics on [IBMX] discovered in the work. Moreover, the biocompatibility of drug carriers can be assessed by the degree to which rods retain stable function in the presence of the carrier molecule, or its monomers.

This thesis consists of an overview and of the following 5 publications:

  1. S. Nymark, H. Heikkinen, C. Haldin, K. Donner, and A. Koskelainen. 2005. Light responses and light adaptation in rat retinal rods at different temperatures. The Journal of Physiology, volume 567, number 3, pages 923-938.
  2. Charlotte Haldin, Soile Nymark, Ann-Christine Aho, Ari Koskelainen, and Kristian Donner. 2009. Rod phototransduction determines the trade-off of temporal integration and speed of vision in dark-adapted toads. The Journal of Neuroscience, volume 29, number 18, pages 5716-5725.
  3. H. Heikkinen, S. Nymark, K. Donner, and A. Koskelainen. 2009. Temperature dependence of dark-adapted sensitivity and light-adaptation in photoreceptors with A1 visual pigments: A comparison of frog L-cones and rods. Vision Research, in press.
  4. H. Heikkinen, S. Nymark, and A. Koskelainen. 2008. Mouse cone photoresponses obtained with electroretinogram from the isolated retina. Vision Research, volume 48, number 2, pages 264-272.
  5. Soile Nymark, Charlotte Haldin, Heikki Tenhu, and Ari Koskelainen. 2006. A new method for measuring free drug concentration: Retinal tissue as a biosensor. Investigative Ophthalmology and Visual Science, volume 47, number 6, pages 2583-2588.

Keywords: photoreceptor, retina, temporal integration, vision, controlled drug release, biocompatibility

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© 2009 Helsinki University of Technology

Last update 2011-05-26