{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:10:19Z","timestamp":1784214619267,"version":"3.55.0"},"reference-count":59,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2022,6,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>\n                      The NLRP3 inflammasome, a cytoplasmic signal transduction complex that regulates inflammation, has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of visual impairment in industrialized countries. We tested the therapeutic effect of anti-inflammatory gene therapy, delivered preventively, in Liver-X-Receptor alpha knockout (\n                      <jats:italic toggle=\"yes\">\n                        LXR\u03b1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      ) mice, which exhibit features of dry AMD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">\n                        LXR\u03b1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice were treated with an adeno-associated virus (AAV) vector that delivers a secretable and cell-penetrating form of the caspase activation and recruitment domain (CARD). A sGFP-FCS-TatCARD-AAV or sGFP-FCS (control) vector was delivered intravitreally to 3\u20135 month-old,\n                      <jats:italic toggle=\"yes\">\n                        LXR\u03b1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice, who were then aged to 15\u201318 months (12\u201313 month treatment). Retinal function and morphology were assessed pre- and post-treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      TatCARD treated\n                      <jats:italic toggle=\"yes\">\n                        LXR\u03b1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice did not show improvement in rod and cone photoreceptor function, measured by dark adapted a- and b-wave amplitudes, and rod-saturated b-wave amplitudes. We found a sex-dependent, significant therapeutic effect in c-wave amplitudes in the TatCARD treated mice, which exhibited maintenance of amplitudes in comparison to the significant decline recorded in the control treated group, indicating a therapeutic effect mediated in part through retinal pigment epithelial (RPE) cells. Additionally, the retinas of the TatCARD treated mice exhibited a significant decline in the concentration of interleukin-1 beta (IL-1\u03b2) concomitant with modulation of several inflammatory cytokines in the retina and RPE-choroid tissues, as measured by ELISA and cytokine array, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Collectively, these results support that anti-inflammatory gene constructs such as AAV-TatCARD may be considered for the treatment of inflammation in AMD and other ocular diseases of the posterior pole in which inflammation may play a role. Furthermore, our findings emphasize the need to carefully consider potential sex-different responses when assessing potential therapies in pre-clinical models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2022.0002","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T10:28:03Z","timestamp":1650536883000},"page":"359-371","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Gene Delivery of a Caspase Activation and Recruitment Domain Improves Retinal Pigment Epithelial Function and Modulates Inflammation in a Mouse Model with Features of Dry Age-Related Macular Degeneration"],"prefix":"10.1177","volume":"38","author":[{"given":"Mayur","family":"Choudhary","sequence":"first","affiliation":[{"name":"Albert Eye Research Institute, Department of Ophthalmology, Duke Eye Center, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristhian J.","family":"Ildefonso","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred S.","family":"Lewin","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goldis","family":"Malek","sequence":"additional","affiliation":[{"name":"Albert Eye Research Institute, Department of Ophthalmology, Duke Eye Center, Duke University School of Medicine, Durham, North Carolina, USA."},{"name":"Department of Pathology, Duke University School of Medicine, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx343"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2019-314422"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00265-2"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15459"},{"key":"e_1_3_6_6_2","first-page":"98","article-title":"Chronic inflammation in cancer development","volume":"2","author":"Multhoff G.","year":"2011","unstructured":"Multhoff G., , Molls M., , and Radons J. 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