Jia-Horung Hung MD , Tanya Jain MD , Anadi Khatri MD , Ba Trung Nguyen MD , Celine Dan-Tam Nguyen BA , Negin Yavari MD , Azadeh Mobasserian MD , Irmak Karaca MD , S. Saeed Mohammadi MD , Ankur Sudhir Gupta MD , Chi Mong Christopher Or MD , Amir Akhavanrezayat MD , Cigdem Yasar MD , Aim-on Saengsirinavin MD , Ngoc Trong Tuong Than MD , Frances Andrea Anover MD , Osama Elaraby MD , Dalia El Feky MD , Woong-Sun Yoo MD, PhD , Xiaoyan Zhang MD, PhD , Quan Dong Nguyen MD, MSc
{"title":"Inherited retinal disease-associated uveitis","authors":"Jia-Horung Hung MD , Tanya Jain MD , Anadi Khatri MD , Ba Trung Nguyen MD , Celine Dan-Tam Nguyen BA , Negin Yavari MD , Azadeh Mobasserian MD , Irmak Karaca MD , S. Saeed Mohammadi MD , Ankur Sudhir Gupta MD , Chi Mong Christopher Or MD , Amir Akhavanrezayat MD , Cigdem Yasar MD , Aim-on Saengsirinavin MD , Ngoc Trong Tuong Than MD , Frances Andrea Anover MD , Osama Elaraby MD , Dalia El Feky MD , Woong-Sun Yoo MD, PhD , Xiaoyan Zhang MD, PhD , Quan Dong Nguyen MD, MSc","doi":"10.1016/j.survophthal.2025.03.011","DOIUrl":null,"url":null,"abstract":"<div><div>Inherited retinal diseases (IRDs) are genetic disorders characterized by progressive photoreceptor function loss, often leading to significant visual impairment. Uveitis has been increasingly recognized in the clinical course of some IRDs. Despite advances in understanding the genetic causes and pathophysiology of IRDs, gaps remain in understanding the roles of inflammation and autoimmunity in IRD and IRD-associated uveitis. This review discusses IRD-associated uveitis, including anterior, intermediate, posterior, and panuveitis, as well as complications such as cystoid macular edema and retinal vasculitis. In patients with IRD-associated uveitis, mutations affecting protein function in cilia or photoreceptor outer segments suggest a universal autoimmune mechanism triggered by the immunogenicity of shedding photoreceptor discs. Notably, in patients where uveitis is the initial sign, CRB1 mutations are often implicated, likely due to the compromised blood-retina barrier function or alterations in the external limiting membrane. Other mechanisms leading to uveitis preceding IRD diagnosis include ALPK1 mutations, which activate the proinflammatory NF-κB pathway, CAPN5 mutations, which lead to dysfunction of the innate and adaptive immune systems, and VCAN1 mutations, which elicit immunogenicity due to irregularities in vitreous modeling. Understanding these mechanisms could enhance the development of innovative treatments that target personalized inflammation pathways in IRDs.</div></div>","PeriodicalId":22102,"journal":{"name":"Survey of ophthalmology","volume":"70 5","pages":"Pages 951-981"},"PeriodicalIF":5.9000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Survey of ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0039625725000578","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Inherited retinal diseases (IRDs) are genetic disorders characterized by progressive photoreceptor function loss, often leading to significant visual impairment. Uveitis has been increasingly recognized in the clinical course of some IRDs. Despite advances in understanding the genetic causes and pathophysiology of IRDs, gaps remain in understanding the roles of inflammation and autoimmunity in IRD and IRD-associated uveitis. This review discusses IRD-associated uveitis, including anterior, intermediate, posterior, and panuveitis, as well as complications such as cystoid macular edema and retinal vasculitis. In patients with IRD-associated uveitis, mutations affecting protein function in cilia or photoreceptor outer segments suggest a universal autoimmune mechanism triggered by the immunogenicity of shedding photoreceptor discs. Notably, in patients where uveitis is the initial sign, CRB1 mutations are often implicated, likely due to the compromised blood-retina barrier function or alterations in the external limiting membrane. Other mechanisms leading to uveitis preceding IRD diagnosis include ALPK1 mutations, which activate the proinflammatory NF-κB pathway, CAPN5 mutations, which lead to dysfunction of the innate and adaptive immune systems, and VCAN1 mutations, which elicit immunogenicity due to irregularities in vitreous modeling. Understanding these mechanisms could enhance the development of innovative treatments that target personalized inflammation pathways in IRDs.
期刊介绍:
Survey of Ophthalmology is a clinically oriented review journal designed to keep ophthalmologists up to date. Comprehensive major review articles, written by experts and stringently refereed, integrate the literature on subjects selected for their clinical importance. Survey also includes feature articles, section reviews, book reviews, and abstracts.