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Antje Biesemeier, Tatjana Taubitz, Ulrich Schraermeyer; Egg or hen: Use of combined light and electron microscopy to reveal whether CC breakdown precedes RPE degeneration in AMD. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3200.
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To investigate different stages of age-related macular degeneration (AMD) and whether choriocapillaris (CC) breakdown precedes retinal pigment epithelial (RPE) degeneration with age and AMD.
Perimacular sections of 11 AMD donor eyes (mean age 83+/-9 y) and 9 controls (68+/-14 y) without known retinal pathology were investigated histologically. Complete 2-3 mm long semithin sections were photographed with 600x magnification by light microscopy. The images were rearranged yielding a panorama overview. By zooming into this panorama different topics were addressed individually and in context with the surrounding tissue, e.g. area of basal deposits, loss of photoreceptors, RPE or CC vessels. Subsequent ultrathin sections were investigated by electron microscopy to yield subcellular information of the same area, e.g. number of fenestrations in CC facing the RPE per µm of endothelium. Where applicable, statistics were performed using the Wilcoxon-Mann-Whitney test for non-parametric statistical hypothesis.
Controls showed complete photoreceptors, confluent RPE monolayer and few basal deposits. Intact CC vessels were lost in about 20 % of Bruch’s membrane length as judged by empty or enlarged pillars (n= 5, mean age 64 y). AMD sections showed areas with loss of photoreceptors, RPE and CC which were directly facing other areas with intact retina-choroid complex. When comparing complete sections, the area occupied by basal deposits was highly increased compared to controls. CC lumina and the number of fenestrations in remaining endothelia were halved in value compared to controls (both p < 0.0001). Areas where either RPE or CC was missing while the other survived were equally abundant. Thus a premier destruction of either one was hard to identify. After gross examination, the sections were classified into 5 stages of retinal degeneration: healthy, early retinal and RPE damage, occult or classic CNV and geographic atrophy to be further investigated.
The data implicate that initial CC breakdown is proposed to precede RPE and retinal degeneration, as judged from comparison of control and AMD sections. Special emphasis should be lead on AMD sections where different stages of degeneration pass over into each other. By comparing these interfaces using the given approach a possible sequence of degenerative steps with ageing and AMD can be revealed.
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