{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T23:14:35Z","timestamp":1772838875716,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie","award":["765441"],"award-info":[{"award-number":["765441"]}]},{"name":"Stiftelsen f\u00f6r Synskadade i f.d. Malm\u00f6hus l\u00e4n","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100010817","name":"Kronprinsessan Margaretas Arbetsn\u00e4mnd f\u00f6r synskadade","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100010817","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010810","name":"\u00d6gonfonden","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100010810","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Royal Physiographic Society of Lund - the Natural Sciences, Medicine and Tech-nology \u2013 Medicine","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Stiftelsen Landsh\u00f6vding Per Westlings minnesfond","award":["95096"],"award-info":[{"award-number":["95096"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The disease retinitis pigmentosa (RP) leads to photoreceptor degeneration by a yet undefined mechanism(s). In several RP mouse models (i.e., rd mice), a high cyclic GMP (cGMP) level within photoreceptors is detected, suggesting that cGMP plays a role in degeneration. The rap guanine exchange factor 4 (EPAC2) is activated by cyclic AMP (cAMP) and is an accepted cGMP-interacting protein. It is unclear whether and how cGMP interacts with EPAC2 in degenerating photoreceptors; we therefore investigated EPAC2 expression and interactions with cGMP and cAMP in retinas of the rd1 and rd10 models for retinal degeneration. EPAC2 expression in the photoreceptor layer increased significantly during rd1 and rd10 degeneration, and an increase in EPAC2 interactions with cGMP but not cAMP in the rd1 was also seen via a proximity ligation assay on histological sections. Retinal explant cultures revealed that pharmacological inhibition of the EPAC2 activity reduced the photoreceptor layer thickness in the rd10 retina, suggesting that EPAC2 inhibition promotes degeneration. Taken together, our results support the hypothesis that high degeneration-related cGMP leads to increased EPAC2 and cGMP interactions, inhibiting EPAC2. By inference, EPAC2 could have neuroprotective capacities that may be exploited in the future.<\/jats:p>","DOI":"10.3390\/ijms23094619","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T05:07:22Z","timestamp":1650604042000},"page":"4619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Enhanced cGMP Interactor Rap Guanine Exchange Factor 4 (EPAC2) Expression and Activity in Degenerating Photoreceptors: A Neuroprotective Response?"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4932-8456","authenticated-orcid":false,"given":"Michel","family":"Rasmussen","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, 22184 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, 22184 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Schwede","sequence":"additional","affiliation":[{"name":"BIOLOG Life Science Institute GmbH & Co. KG, 28199 Bremen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Ekstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, 22184 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,21]]},"reference":[{"key":"ref_1","unstructured":"Fahim, A.T., Daiger, S.P., and Weleber, R.G. (2020, September 23). Nonsyndromic Retinitis Pigmentosa Overview. GeneReviews\u00ae, Available online: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20301590."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2174\/138920211795860116","article-title":"Diagnostic Challenges in Retinitis Pigmentosa: Genotypic Multiplicity and Phenotypic Variability","volume":"12","author":"Chang","year":"2011","journal-title":"Curr. 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