Ghost vessels in the eye: Cell free choriocapillaris domains in atrophic age-related macular degeneration

• Published in: Experimental eye research 2024-11, Vol.248, p.110128, Article 110128
• Main Authors: Mullins, Robert F., Flamme-Wiese, Miles J., Navratil, Emma M., Boese, Erin A., Varzavand, Katayoun, Riker, Megan J., Wang, Kai, Stone, Edwin M., Tucker, Budd A.
• Format: Article
• Language: English
• Subjects: Age-related macular degeneration; Aged; Aged, 80 and over; Aging; Capillaries - pathology; Choriocapillaris; Choroid - blood supply; Choroid - pathology; Complement Factor H - genetics; Female; Genotype; Geographic Atrophy - genetics; Humans; Macular Degeneration - genetics; Macular Degeneration - metabolism; Macular Degeneration - pathology; Male; Middle Aged; Retinal Pigment Epithelium - pathology; Tissue Donors
• ISSN: 0014-4835; 1096-0007; 1096-0007
• DOI: 10.1016/j.exer.2024.110128

The choriocapillaris is a dense vascular bed in the inner choroid that supplies the photoreceptor cells and retinal pigment epithelium (RPE). While loss of choriocapillaris density has been described in association with age-related macular degeneration (AMD), whether these changes are primary or secondary to RPE degenerative changes in AMD has been debated. In this study we characterized choriocapillaris loss by quantifying “ghost” vessels in a series of 99 human donor maculae labeled with the UEA-I lectin, and found significant increases in early-intermediate AMD and a greater difference in geographic atrophy in areas with intact RPE. Eyes were genotyped at the CFH Tyr402His locus, and those homozygous for the His allele showed significantly more ghost vessels than those with other genotypes. When only non-AMD eyes were evaluated, His homozygotes had increased ghost vessel density but this trend did not reach statistical significance. These results support the notion that choriocapillaris death often precedes RPE degeneration in AMD and that this loss is an important therapeutic consideration for AMD. •Ghost vessels in the choriocapillaris are nonperfused lumens that persist after endothelial death.•Density of ghost vessels was measured in human donor maculae with early to advanced AMD and controls.•Genotyping was also performed at the CFH Y402H locus.•Advancing AMD and to a lesser extent genotype was associated with density of ghost vessels.•Relevance to therapy is discussed.