{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:57:18Z","timestamp":1781200638554,"version":"3.54.1"},"reference-count":62,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["EY022383 and EY035549 and P30EY0017675"],"award-info":[{"award-number":["EY022383 and EY035549 and P30EY0017675"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Oxidative stress has a major pathogenic role in diabetic retinopathy (DR), and neuroretina dysfunction is recognized as an early and important problem. Soluble guanylate cyclase (sGC) has been implicated for its neuroprotective effects in the central nervous system, but its role in the retina remains unclear. Here, we demonstrated in healthy human and rodent retinas the expression of sGC subunits GUCY1A1 and GUCY1B1 in vascular cells and neuronal elements, including retinal ganglion, bipolar, and amacrine cells. We provided evidence using in\u00a0vitro and in\u00a0vivo studies that sGC function is impaired by oxidative stress\u2013induced damage in the retina. The sGC activator runcaciguat activated sGC in multiple retinal cell types and counteracted the inhibitory effect of damage induced by oxidative stress on the retina and retinal cells. In the rat retinal ischemia-reperfusion model, runcaciguat treatment improved neuroretinal and visual function as measured by electroretinography and optokinetic tracking and resulted in retinal morphologic improvement. In the streptozotocin-induced diabetic rat model, runcaciguat significantly improved neuroretinal function and improved inner plexiform layer thickness. These studies suggest that sGC signaling is involved in neuroretinal function and vision and that diabetes negatively affects this pathway, supporting restoring sGC activation as a novel therapy for early DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Soluble guanylate cyclase (sGC) subunits are expressed in retinal vascular and neuronal cells. Runcaciguat activates sGC impaired by oxidative stress in\u00a0vitro and in\u00a0vivo. Runcaciguat improves retinal neuronal function and morphology in rat models of ischemia-reperfusion and streptozotocin-induced diabetes. Restoring sGC activity is a novel therapeutic target for early diabetic retinopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db24-0739","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T12:14:02Z","timestamp":1746620042000},"page":"1220-1232","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":1,"title":["Neuroprotective Effect of a Novel Soluble Guanylate Cyclase Activator Runcaciguat in Diabetic and Ischemic Retinopathy"],"prefix":"10.2337","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1917-373X","authenticated-orcid":false,"given":"Elia J.","family":"Duh","sequence":"first","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Xu","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongkwan","family":"Cho","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Wu","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Schubert","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal 2 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Terjung","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal 2 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Baschiera","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal 2 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Zhou","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Lee","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyiran","family":"Xie","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyan","family":"Hui","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Guerra","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Mertz","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute, Johns Hopkins University School of Medicine 1 , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4974-3828","authenticated-orcid":false,"given":"Khaled","family":"Nassar","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal 2 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"2026061113030338600_B1","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.2337\/dc15-2171","article-title":"Global estimates on the number of people blind or visually impaired by diabetic retinopathy: a meta-analysis from 1990 to 2010","volume":"39","author":"Leasher","year":"2016","journal-title":"Diabetes Care"},{"key":"2026061113030338600_B2","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/S0140-6736(08)61411-7","article-title":"Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial","volume":"372","author":"Sj\u00f8lie","year":"2008","journal-title":"Lancet"},{"key":"2026061113030338600_B3","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1016\/S0140-6736(08)61412-9","article-title":"Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials","volume":"372","author":"Chaturvedi","year":"2008","journal-title":"Lancet"},{"key":"2026061113030338600_B4","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1097\/IAE.0b013e3182111669","article-title":"Oral protein kinase c \u03b2 inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the Protein Kinase C \u03b2 Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C \u03b2 Inhibitor-Diabetic Retinopathy Study 2","volume":"31","author":"Aiello","year":"2011","journal-title":"Retina"},{"key":"2026061113030338600_B5","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cmet.2012.11.012","article-title":"Vascular complications of diabetes: mechanisms of injury and protective 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