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Retinoic Acid Receptor-Related Orphan Receptors (RORs) in Eye Development and Disease
Felix Yemanyi1, Kiran Bora1, Alexandra K Blomfield1
1Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Abstract:
The retinoic acid receptor-related orphan receptors (RORs) are ligand-mediated transcription factors with important biological roles in regulating circadian rhythms, metabolism, immunity, angiogenesis, inflammation, and development. They belong to the superfamily of nuclear receptors and include three family members: RORα, RORβ, and RORγ. Currently identified ROR ligands include cholesterol and cholesterol derivatives for RORα and RORγ, and stearic acid and all-trans retinoic acid for RORβ. Aberrant signaling of the RORs is involved in the pathogenesis of several human diseases including autoimmune diseases, metabolic disorders, and certain cancers. In the eye, RORs regulate normal development of the lens and the retina, and also contribute to potentially blinding eye diseases, especially retinal vascular diseases. Here, we review the role of RORs in eye development and disease to highlight their potential as druggable targets for therapeutic development in retinal vascular and degenerative diseases.
Insights
Retinoic acid receptor-related orphan receptors (RORs) are crucial for eye development and function. This review highlights their role in retinal diseases and potential as therapeutic targets.
Area of Science:
- Molecular Biology
- Developmental Biology
- Ophthalmology
Background:
- Retinoic acid receptor-related orphan receptors (RORs) are nuclear receptors regulating circadian rhythms, metabolism, immunity, and development.
- RORs comprise three members (RORα, RORβ, RORγ) with distinct ligands, including cholesterol and retinoic acid derivatives.
- Aberrant ROR signaling is implicated in autoimmune diseases, metabolic disorders, and cancers.
Approach:
- This review synthesizes current research on the function of RORs in ocular development.
- It examines the involvement of RORs in the pathogenesis of retinal vascular and degenerative diseases.
- The review underscores the therapeutic potential of targeting RORs for eye conditions.
Key Points:
- RORs are essential for normal lens and retinal development.
- Dysregulation of RORs contributes to blinding eye diseases, particularly retinal vascular diseases.
- RORs represent promising druggable targets for treating retinal vascular and degenerative diseases.
Conclusions:
- RORs play a critical role in maintaining ocular health and development.
- Targeting RORs offers a potential therapeutic strategy for various retinal diseases.
- Further research into ROR-targeted therapies could lead to novel treatments for vision impairment.
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