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Genetic Loss of RORα Impairs Visual Function With Rod Bipolar Cell Degeneration In Mice.

Kiran Bora¹, Chi-Hsiu Liu¹, Neetu Kushwah¹

¹Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States.

Investigative Ophthalmology & Visual Science

|August 8, 2025

Summary

Retinoic acid receptor-related orphan receptor alpha (RORα) deficiency impairs mouse vision by damaging rod bipolar cells. This highlights RORα's crucial role in maintaining retinal structure and function, suggesting it as a therapeutic target for vision loss.

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Area of Science:

Ophthalmology and visual neuroscience
Molecular and cellular biology
Genetics and developmental biology

Background:

Retinoic acid receptor-related orphan receptor alpha (RORα) is a nuclear receptor vital for eye development.
Genetic variations in RORα are associated with age-related macular degeneration, but its direct role in visual function remains unclear.

Purpose of the Study:

To investigate the role of RORα in regulating visual function.
To examine the impact of RORα deficiency on retinal structure and gene expression in mice.

Main Methods:

Visual function was assessed using electroretinography (ERG) in RORα-deficient (Rorasg/sg) mice and wild-type controls.
Retinal localization of RORα, rod bipolar cell morphology, retinal thickness, gliosis, and visual transduction gene expression were analyzed.

Main Results:

RORα deficiency significantly impaired visual function, evidenced by reduced ERG b-wave amplitude, indicating bipolar cell dysfunction.
Rorasg/sg mice exhibited degeneration of rod bipolar cells, retinal gliosis, and retinal thinning, which worsened with age.
Upregulation of phototransduction and bipolar cell depolarization genes suggested compensatory signaling remodeling.

Conclusions:

RORα is essential for the structural and functional integrity of rod bipolar cells.
RORα deficiency leads to progressive retinal degeneration and visual impairment.
RORα represents a potential therapeutic target for retinal degenerative diseases characterized by bipolar cell deficits.