Abstract
Purpose :
The macula is specifically affected in many retinal diseases; including diabetic macula oedema, Stargardt macular dystrophy and Macular Telangiectasia type 2, among others. This may be due to differential distribution of cell types (for example, rods versus cones), but relatively little is known about how the differential distribution of cells affects the metabolism of the retina. Here we present a global metabolomic analysis of macula versus peripheral retina.
Methods :
Macula and peripheral samples of retinal tissue were dissected from light adapted Macaca mulatta. Samples of each region from 7 eyes were analysed by non-targeted mass-spectrometry (MS) analysis (Metabolon Inc.) using ultrahigh-performance liquid chromatography-tandem MS.
Results :
We detected a total of 422 metabolites in the primate retina. Amongst the metabolites providing the strongest MS signals were creatine, N-acetylaspartate (NAA), taurine, glycerophosphorylcholine (GPC), choline, sorbitol, betaine and myo-inositol. This is likely due to the high abundance of these metabolites in retinal tissue. All 7 of these metabolites are also known to function as endogenous osmolytes and are, therefore, likely to contribute to osmotic homeostasis in the retina.
110 metabolites showed differential abundance in the macula versus the peripheral retina. The most strongly enriched metabolites in the macula were 2 carotene diols; most likely lutein and zeaxanthin. The most enriched metabolic pathway in the macula was pyrimidine metabolism, whilst the most depleted pathway was that of sphingolipid metabolism. Furthermore, several purines and phosphatidylethanolamines were also reduced in the macula.
Conclusions :
The underlying reasons for the differential abundance of these metabolites are yet to be established. Nevertheless, our data demonstrate regional specialisation of metabolic pathways in the primate retina, which may contribute to regional susceptibilities observed in multiple diseases.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.