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In this study, we investigated the role of ubiquitin protein ligase E3D (UBE3D) in aging and degeneration in mouse retina. Conditional knockout of\n                    <jats:italic>Ube3d<\/jats:italic>\n                    in the retinal pigment epithelium (RPE) of mice led to progressive and irregular fundus lesions, attenuation of the retinal vascular system, and age\u2010associated deterioration of rod and cone responses. Simultaneously, RPE\u2010specific\n                    <jats:italic>Ube3d<\/jats:italic>\n                    knockout mice also presented morphological changes similar to the histopathological characteristics of human AMD, in which a defective UPS led to RPE abnormalities such as phagocytosis or degradation of metabolites, the interaction with photoreceptor outer segment, and the transport of nutrients or waste products with choroidal capillaries via Bruch's membrane. Moreover, conditional loss of\n                    <jats:italic>Ube3d<\/jats:italic>\n                    resulted in aberrant molecular characterizations associated with the autophagy\u2013lysosomal pathway, oxidative stress damage, and cell\u2010cycle regulation, which are implicated in AMD pathology. Thus, our findings strengthen and expand the impact of UPS dysfunction on retinal pathophysiology during aging, indicating that genetic\n                    <jats:italic>Ube3d<\/jats:italic>\n                    deficiency in the RPE could lead to the abnormal formation of pigment deposits and secondary fundus alterations. \u00a9 2023 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6201","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T06:46:25Z","timestamp":1695969985000},"page":"442-454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Conditional loss of\n                    <scp>\n                      <i>Ube3d<\/i>\n                    <\/scp>\n                    in the retinal pigment epithelium accelerates age\u2010associated alterations in the retina of mice"],"prefix":"10.1002","volume":"261","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9420-8109","authenticated-orcid":false,"given":"Tianchang","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Peking University People's Hospital, Eye Diseases and Optometry Institute  Beijing PR China"},{"name":"Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases  Beijing PR China"},{"name":"College of Optometry Peking University Health Science Center  Beijing PR China"},{"name":"Department of Ophthalmology The First Affiliated Hospital of Anhui Medical University  Hefei PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-5422","authenticated-orcid":false,"given":"Ningda","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Peking University 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