Hlutverk púrína í stjórnun á losun frumuboðefna og jónaflutninga um litþekju augans - verkefni lokið
Fréttatilkynning verkefnisstjóra
The main aim of this project was to gain further understanding of the role of purines in the physiological function of the retinal pigment epithelium (RPE) in controlling the release of cytokines and the transepithelial ion transport, and which thus may shed light on diseases that affect the retina and the RPE.
Heiti verkefnis: Hlutverk
púrína í stjórnun á losun frumuboðefna og jónaflutninga um litþekju augans
Verkefnisstjóri: Þór Eysteinsson, Háskóla Íslands
Tegund styrks: Verkefnisstyrkur
Styrktímabil: 2013-2015
Fjárhæð styrks: 14,15 millj. kr. alls
Tilvísunarnúmer Rannís: 130683
Experiments on transepithelial transport across a mouse RPE “native” preparation were carried out, focusing on ion channels, primarily Cl- and K+ channels, that may be involved. It was found for the first time that the role of K+ channels in the mouse RPE ion transport is similar to that found in other vertebrate species. However, the Cl- channels on these cells in the mouse have an unusual function, since Ca++-dependent chloride channels on the apical side of the RPE mediate a large chloride current, while in most species Cl- channels on the basolateral side are more important. The CFTR chloride channel appears to play a lesser role, and mediate short-circuit current changes that are only transient. Purine receptors, both the P2X and P2Y subtypes, do affect transepithelial transport across the mouse RPE, but the P2X7 subtype of receptors and some unknown P2Y subtypes appear to be the most important of these. But when these receptors are stimulated or blocked the changes that occur in ion transport are proportionately small. Experiments with culturing mouse RPE cells as polarized monolayers on membranes, to measure cytokine release from the apical and basolateral side separately, have not been successful so far, so the effects of stimulating purine receptors that are clearly present on these cells on cytokine release is still unknown. The work demonstrates that the mouse RPE can be used as a feasible model to study transport physiology, and thus ion transport across this tissue in mouse models of eye diseases, including age-related macular degeneration.
The following publications and presentations are the outputs of the project so far:
Skarphéðinsdóttir, S.B.: The role of purines and chloride channels in the function of the mouse retinal pigment epithelium. MSc thesis, School of health Sciences, University of Iceland, 2015.
Skarphedinsdottir, S.B., Eysteinsson, T., Arnason, S.S. Ion transport mechanisms measured across the mouse retinal pigment epithelium in vitro. Manuscript in preparation (enclosed)
Arnason, S.S., Skarphedinsdottir, S.B., Eysteinsson, T. Ion transport across the murine retinal pigment epithelium. Experimental Biology meeting, Boston 2013. The FASEB Journal, 27:1148.13, 2013.
Eysteinsson, T., Skarphedinsdottir, S.B., Arnason, S.S. Adrenergic but not purinergic receptors affect ion transport across the mouse retinal pigment epithelium. ARVO annual meeting, Seattle, Washington, May 2013, Presentation Number: 6348/D0219.
Skarphedinsdottir, S.B., Eysteinsson, T., Arnason, S.S. The role of Cl- channels in ion transport across the apical and basolateral sides of the mouse retinal pigment epithelium. EVER annual meeting, Nice, F010, 2013.
Arnason, S.S., Skarphedinsdottir, S.B., Eysteinsson, T. The role of purinergic P2X receptors and Ca++ dependent chloride channels in ion transport of mouse retinal pigment epithelium. ARVO annual meeting, Orlando, Florida, May 2014, Presentation Number: 1882/B0147.
García Llorca, A., Ögmundsdottir, M.H, Steingrimsson, E., Eysteinsson, T. Mutations in the Mitf gene affect autophagy in mouse RPE cells. ARVO annual meeting, Seattle, Wash., May 2016, 6037/D0256.
Garcia Llorca, A., Ogmundsdóttir, M.H., Steingrimsson, E. and Eysteinsson, T. (2016), Autophagy is affected by Mitf in mouse primary RPE cells. Acta Ophthalmol, 94: n/a. doi:10.1111/j.1755-3768.2016.0605.
