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Inherited retinal disease-associated uveitis.

Jia-Horung Hung1, Tanya Jain2, Anadi Khatri3

  • 1Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA; Department of Genomic Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Survey of Ophthalmology
|March 29, 2025
PubMed
Summary

Inherited retinal diseases (IRDs) can cause uveitis through autoimmune responses to photoreceptor damage. Understanding these genetic triggers is key to developing targeted treatments for vision loss.

Keywords:
Anterior uveitisCystoid macular edemaInherited retinal diseaseIntermediate uveitisPanuveitisPosterior uveitisRetinal vasculitisRetinitis pigmentosa

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Area of Science:

  • Ophthalmology
  • Genetics
  • Immunology

Background:

  • Inherited retinal diseases (IRDs) cause progressive vision loss due to photoreceptor dysfunction.
  • Uveitis is increasingly observed in patients with IRDs, highlighting the role of inflammation.
  • The interplay between IRDs, inflammation, and autoimmunity requires further investigation.

Purpose of the Study:

  • To review the mechanisms of uveitis associated with inherited retinal diseases.
  • To explore the genetic underpinnings and autoimmune triggers of IRD-associated uveitis.
  • To discuss potential therapeutic strategies targeting inflammatory pathways.

Main Methods:

  • Literature review of studies on IRDs and associated uveitis.
  • Analysis of genetic mutations implicated in IRD-associated uveitis.
  • Discussion of proposed autoimmune mechanisms and clinical presentations.

Main Results:

  • Mutations in genes affecting cilia or photoreceptor outer segments suggest a common autoimmune mechanism triggered by photoreceptor disc shedding.
  • CRB1 mutations are frequently linked to uveitis as an initial symptom, potentially due to blood-retina barrier disruption.
  • Other genetic mutations (ALPK1, CAPN5, VCAN1) activate inflammatory pathways or disrupt immune function, leading to uveitis.

Conclusions:

  • Autoimmunity, triggered by photoreceptor damage, is a significant factor in IRD-associated uveitis.
  • Specific genetic mutations provide insights into the diverse mechanisms driving uveitis in IRDs.
  • Targeting personalized inflammation pathways holds promise for novel therapeutic interventions in IRDs.