gms | German Medical Science

Background: In normal human macula, we investigated with comprehensive molecular and ultrastructural technologies an ecosystem that contributes to drusen lipids (PMID 30357337). Two features of high-risk drusen and their precursors in Bruch’s membrane implicate macular biology: enrichment in the fatty acid linoleate signifying a dietary source; epidemiologic localization within the central subfield and inner ring of the ETDRS fundus grading grid, suggesting a relationship with foveal cone photoreceptors and supporting Müller glia.

Methods: To map mass/ charge (m/z) signals from tissue lipids without using labels or stains, eyes from donors older than 80 years of age and recovered within 6 hours of death were cryosectioned for imaging mass spectrometry. To determine the proportion of retinal layers occupied by Müller glia, one eye from a 21-year-old organ donor was preserved at the withdrawal of life support and serially thin-sectioned through the fovea for volume electron microscopy.

Results: Hundreds of m/z were detected. Many lipids were identifiable via bioinformatics. Among 6 m/z patterns specific to single or grouped retinal layers, a bowtie pattern was unique to the fovea and adjacent parafovea. High signal intensity in the foveal center, HFL, IPL, and NFL of the bowtie resembled the distribution of xanthophyll carotenoids described in macaque retina (PMID 6724837). The volume fraction occupied by Müller glia is 80-90% in the foveal floor and HFL and less than 50% in cellular layers.

Conclusion: The bowtie m/z pattern was associated with a population of human macular cells resembling Müller glia, suggesting a distinctive lipid profile for these cells. Müller glia processes are abundant in retinal layers known to have high xanthophyll content. Data are consistent with (but do not prove) a hypothesis that soft druse lipids may be remainders from the dietary delivery of xanthophyll carotenoids used by specialized Müller glia to sustain foveal cones.