Abstract
Purpose :
Continued light sensitivity necessitates the regeneration of 11-cis-retinal via a series of enzyme-catalyzed steps within the visual cycle. During this process vitamin A aldehyde is shepherded within photoreceptors and retinal pigment epithelial cells by retinoid-binding proteins and NRPE to facilitate retinoid trafficking, to prevent non-specific aldehyde reactivity and to conserve the 11-cis configuration. Least understood is a Schiff base adduct (A1T) that forms non-enzymatically and reversibly from reactions between taurine and vitamin A-aldehyde and is abundant in neural retina of humans and mice.
Methods :
Retinoids (derivatized with O-ethylhydroxylamine (100 mM) in DPBS) and bisretinoids, taurine and β-alanine (derivatived with NBD-F) were quantified by HPLC and UPLC with reference to authentic standards. A1T was synthesized by reacting retinaldehyde with taurine (1:1 molar ratio of retinal isomers and taurine) in dehydrated methanol containing sodium methoxide. ONL area was calculated as the sum of the ONL thicknesses in superior and inferior retina (0.2–2.0 mm) multiplied by the measurement interval of 200 microns.
Results :
Reduction in cellular taurine by treatment with the taurine transport inhibitor β-alanine (in drinking water, 2%; 2 months) accentuated the thinning of outer nuclear layer (ONL) expected in albino Abca4-/- mice. β-alanine-treatment reduced bisretinoid levels. When mice were treated with taurine (2.5% in drinking water for 2, 4 and 6 months) ONL thinning in albino Abca4-/- mice was reduced.
Conclusions :
We previously observed that A1T is more abundant under conditions in which 11-cis-retinaldehyde is present at higher levels, including black versus albino mice, dark-adapted versus light-adapted mice and mice carrying the Rpe65-Leu450 versus Rpe65-450Met variant. The accentuated ONL thinning indicative of photoreceptor cell loss, is consistent with previous reports of photoreceptor cell death in the presence of taurine deficiency; perhaps the worsening of ONL thinning occurs due to inadequate 11-cis-retinal handling. The reduction in bisretinoid levels with b-alanine treatment suggests that the intent of A1T formation is not to protect against unwanted bisretinoid formation as might be supposed. Rather A1T may serve to preserve retinaldehyde.
This is a 2021 ARVO Annual Meeting abstract.