Abstract
Purpose :
While transport of all-trans retinol (ROL) into the eye from serum ROL bound to retinol binding protein 4 (ROL-RBP4) is maintained through the ocular vitamin A receptor STRA6, maintenance of serum ROL-RBP4 equilibrium by the liver is facilitated by the novel analogous systemic vitamin A receptor RBPR2. Our previous findings indicate the importance of RBPR2 in the facilitation of visual function, despite it being a systemic ROL transporter. Here, we present an expanded investigation towards the importance of RBPR2 and the diet on systemic ROL maintenance for visual function.
Methods :
Rbpr2 KO mice were fed with either a vitamin A sufficient (VAS) diet, or a vitamin A deficient (VAD) diet for up to 6 months. At 3- and 6-month age, Rbpr2 KO and WT mice were subjected to scotopic ERG analysis, and photopic spectrum specific ERG analysis. Various non-ocular tissues and eyes were extracted for normal phase HPLC analysis of retinyl esters, retinaldehyde isomers, and all-trans retinol.
Results :
Rbpr2 KO mice on either diet displayed lower scotopic responses when compared to wild type mice. Moreover, Rbpr2 KO mice fed with a VAD diet displayed lower responses when compared to Rbpr2 KO mice fed with a VAS diet. Rbpr2 KO mice fed with a VAD diet displayed lower UV-wavelength and mid-wavelength cone responses when compared to Rbpr2 KO mice fed with a VAS diet. HPLC analysis of systemic organs revealed that Rbpr2 KO mice displayed lower vitamin A content when compared to wild type mice, and Rbpr2 KO mice on a VAD diet displayed even lower vitamin A content when compared mice on a VAS diet.
Conclusions :
Our results indicate that systemic vitamin A content is reduced in peripheral tissues, including the eye in Rbpr2 KO mice. Loss of RBPR2 subsequently leads to the disruption of both rod and cone based visual function in these mice. The VAD condition critically limits the other redundant pathways of vitamin A transport. In this condition, mice lacking RBPR2 and under vitamin A restriction are more susceptible, wherein, visual function is even further disrupted and systemic vitamin A content is further reduced in Rbpr2 KO mice under VAD diet. Thus, both genetics and the diet play an important role in maintain visual function in mammals.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.