Abstract
Purpose :
Taurine is an endogenous sulfur-containing amino acid that carries a primary amine. Taurine is not incorporated into protein but concentrations are particularly high in retina. The function of taurine in retina is not clear. Here we sought to understand the mechanisms by which taurine may protect retina by reducing the formation of RPE lipofuscin bisretinoid.
Methods :
Retinaldehyde-taurine adducts and bisretinoids were measured by UPLC-MS. Albino and agouti Abca4 null mutant mice (Abca4-/-, Rpe65-Leu450) mice were studied. Non-invasive quantitative fundus autofluorescence (qAF, 488 nm) served as an indirect measure of bisretinoid lipofuscin of retina.
Results :
We detected the reversible Schiff base adduct of one retinaldehyde and taurine (A1T) in human, mouse and bovine retina by UPLC-MS. We did not detect A2-taurine, the non-reversible undesirable condensation product of taurine with 2 vitamin A-aldehyde. In assays utilizing isolated bovine outer segments with the addition of taurine and all-trans-retinal, A1-taurine formed and production of the bisretinoids all-trans-retinal dimer and A2PE (A2E precursor) were reduced. By non-invasive quantitative fundus autofluorescence (qAF) (488 nm excitation; Heidelberg Spectralis) oral delivery of taurine (25 grams per liter in drinking water) to agouti Abca4-/- mice (age 1 to 4 months) resulted in a 19.5% reduction in qAF versus control (1.08±0.09 qAF units versus 0.87±0.05 qAF units; mean±SEM). Taurine deficiency induced in albino Abca4-/- mice by a competitive inhibitor guanidinoethyl sulfonate (GES; 10 grams per liter in drinking water; age 1 to 3 months) of the Na+-dependent taurine transporter resulted in an increase in qAF (GES: 0.91±0.04 qAF units; control: 0.77±0.03 qAF units; mean±SEM, p < 0.05).
Conclusions :
The formation of A1-taurine indicates that taurine can sequester retinaldehyde. Temporary sequestration has the potential to suppress bisretinoid formation. For instance, sequestration of retinaldehyde by taurine could aid the reduction of the aldehyde moiety to a non-toxic alcohol by retinol dehydrogenase. Accordingly, we observed a reduction in qAF.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.