Abstract
Purpose :
The omega-3 family member docosahexaenoic acid (DHA, 22:6) and its very-long-chain polyunsaturated fatty acid derivatives (VLC-PUFAs, ≥C28), which are concentrated in photoreceptors and necessary for vision, recycle as components of a phospholipid during daily photoreceptor membrane renewal. We identified a rod cell-selective and topographic-specific location of a phosphatidylcholine (PC) that contains these fatty acids in the human retina, which is lost with the progression of AMD.
Methods :
Human donor eyes were sectioned and processed for MALDI-IMS (Waters) or lipids were extracted for LC-MS/MS using Synapt G2-Si analysis (Waters). Regions of interest on the MALDI sections were used to create differential spectra, prominent peaks detected, and m/z molecules identified and localized. Section images were constructed with BioMap, and full fragmentation was confirmed for lipid structure.
Results :
Macular and peripheral retina differential spectra revealed regional PC abundance and peripheral PC-VLC-PUFA loss in AMD, including important photoreceptor PC-VLC-PUFA loss near the macula (PC34:5/22:6; PC34:4/22:6 and PC34:6/22:6). Peripheral and macular punches for LC-MS/MS characterization of phospholipids containing DHA showed a lower abundance of 54 and 56 carbons in AMD periphery compared to normal periphery, while the AMD and normal macula had similar abundance.
Conclusions :
VLC-PUFAs are the precursors of the neuroprotective, pro-homeostatic elovanoids; their reduction occurs with impaired synthesis. VLC-PUFAs are abundant in rods (periphery); reduction in AMD may affect rod survival. Conversely, events triggering AMD may impair rod VLC-PUFA synthesis. If 22:6 abundance is decreased in AMD, causing a VLC-PUFA decrease, peripheral rods may show the first changes in the retinal 22:6/VLC-PUFA lipidome, perturbing possible signaling between photoreceptor cells of different regions.
This abstract was presented at the 2023 ARVO Imaging in the Eye Conference, held in New Orleans, LA, April 21-22, 2023.