C20D3-Vitamin A Prevents Retinal Pigment Epithelium Atrophic Changes in a Mouse Model.

Abstract

Purpose:

This study aimed to evaluate the contribution of vitamin A dimerization to retinal pigment epithelium (RPE) atrophic changes. Leading causes of irreversible blindness, including Stargardt disease and age-related macular degeneration (AMD), occur as a result of atrophic changes in RPE. The cause of the RPE atrophic changes is not apparent. During the vitamin A cycle, vitamin A dimerizes, leading to vitamin A cycle byproducts, such as vitamin A dimers, in the RPE.

Methods:

To study the consequence of vitamin A dimerization to RPE atrophic changes, we used a rodent model with accelerated vitamin A dimerization, Abca4-/-/Rdh8-/- mice, and the vitamin A analog C20D3-vitamin A to selectively ameliorate the accelerated rate of vitamin A dimerization.

Results:

We show that ameliorating the rate of vitamin A dimerization with C20D3-vitamin A mitigates pathological changes observed in the prodromal phase of the most prevalent retinal degenerative diseases, including fundus autofluorescence changes, dark adaptation delays, and signature RPE atrophic changes.

Conclusions:

Data demonstrate that the dimerization of vitamin A during the vitamin A cycle is sufficient alone to cause the prerequisite RPE atrophic changes thought to be responsible for the leading causes of irreversible blindness and that correcting the dimerization rate with C20D3-vitamin A may be sufficient to prevent the RPE atrophic changes.

Translational Relevance:

Preventing the dimerization of vitamin A with the vitamin A analog C20D3-vitamin A may be sufficient to alter the clinical course of the most prevalent forms of blindness, including Stargardt disease and age-related macular degeneration (AMD).

• Authors: Dan Zhang, Kiera Robinson, Ilyas Washington
• Journal: Translational vision science & technology (Transl Vis Sci Technol) Vol. 10 Issue 14 Pg. 8 (12 01 2021) ISSN: 2164-2591 [Electronic] United States
• PMID: 34878528 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• ATP-Binding Cassette Transporters
• Abca4 protein, mouse
• Vitamin A

Topics

• ATP-Binding Cassette Transporters
• Animals
• Macular Degeneration (genetics, prevention & control)
• Mice
• Retinal Degeneration
• Retinal Pigment Epithelium (metabolism)
• Stargardt Disease
• Vitamin A (metabolism)