September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Degenerating photoreceptors in Retinitis pigmentosa models release cGMP. A way of self protection?
Author Affiliations & Notes
  • Patricia Veiga-Crespo
    Clinical Sciences Lund, Ophthalmology, Lund University, Lund, Sweden
  • Hodan Abdshill
    Clinical Sciences Lund, Ophthalmology, Lund University, Lund, Sweden
  • Birgitta Sandström
    Clinical Sciences Lund, Ophthalmology, Lund University, Lund, Sweden
  • Volkhard Kaever
    Research Core Unit Metabolomics , Hannover Medical School, Hannover, Germany
  • Valeria Marigo
    Università degli studi di Modena e Reggio Emilia, Modena, Italy
  • Francois Paquet-Durand
    Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Tubingen, Germany
  • Frank Schwede
    Biolog Life Science Institute, Bremen, Germany
  • Andreas Rentsch
    Biolog Life Science Institute, Bremen, Germany
  • Per A R Ekström
    Clinical Sciences Lund, Ophthalmology, Lund University, Lund, Sweden
  • Footnotes
    Commercial Relationships   Patricia Veiga-Crespo, None; Hodan Abdshill, None; Birgitta Sandström, None; Volkhard Kaever, None; Valeria Marigo, None; Francois Paquet-Durand, None; Frank Schwede, Biolog Life Science Institute (E); Andreas Rentsch, Biolog Life Science Institute (E); Per Ekström, None
  • Footnotes
    Support  FP7 HEALTH-F2-2012-304963 “DRUGSFORD”; Ögonfonden; KMA; Stiftelsen Synskadade i f.d. Malmöhus län; Stiftelsen Olle Engkvist Byggmästare
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2731. doi:
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      Patricia Veiga-Crespo, Hodan Abdshill, Birgitta Sandström, Volkhard Kaever, Valeria Marigo, Francois Paquet-Durand, Frank Schwede, Andreas Rentsch, Per A R Ekström; Degenerating photoreceptors in Retinitis pigmentosa models release cGMP. A way of self protection?. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2731.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : The inherited retinal degeneration Retinitis pigmentosa (RP) has unknown mechanisms. Many RP models show increased levels of photoreceptor cGMP, suggesting high cGMP as a degeneration factor. We speculated that RP photoreceptors may try to extrude excess cGMP as a means of self protection, and hence here analysed the presence of cGMP in medium conditioned by degenerating RP retinas.

Methods : Relevantly aged mouse RP model or healthy retinas were cultured as organotypic explants for various timepoints, with medium changed every second day. Spent medium was used for cGMP measurements via ELISA based kits. cGMP in the medium was confirmed by HPLC and mass spectrometry. Compounds with effects on tentative cGMP transporters, or on cGMP-dependent protein kinase (PKG) or cyclic nucleotide gated channels (CNGs), were tried on the cultures. Conditioned medium from cultures of rod-like cells from retinal stem cells was also tested

Results : Medium conditioned by retinas from rd1, rd10 and rd2 mice, all known to accumulate photoreceptor cGMP, had elevated levels of cGMP, with different release profiles. The cGMP into medium/retina was for rd1 measured to 277±3 pmoles (mean±SEM, n=4) between 4 and 6 days in vitro (DIV) from postnatal day 5, and for healthy retina to 57±5 (n=9, p<0.001). Treatment between 2 and 6 DIV with probenecid, a blocker of some transporter proteins, reduced rd1 medium cGMP to about 22 % of untreated at 6 DIV. Furthermore, cGMP analogues with effects on CNGs and/or PKG also altered the cGMP level in the medium. Highest values for rd2 (PN5+9DIV, n=4) and rd10 (PN7+10DIV, n=4) were estimated to 200±12 and 244±5 pmoles/retina, respectively. Conditioned medium from rod-like cells likewise contained cGMP.

Conclusions : Compared to healthy retinas, explants from three RP models all increased the levels of cGMP in their conditioned medium, suggesting that cGMP finds its way out of the diseased photoreceptor cells. This could occur via some transporter mechanism, since probenecid reduced the extracellular cGMP levels, and may thus represent a controlled release rather than a passive leakage. The release also has a relation to cGMP interactions, since cGMP analogues were able to modulate the extracellular cGMP levels. cGMP release could be a component in the degeneration machinery, with possible relevance for the outcome of the disease.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


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