Dataset Information

Histopathological Insights Into Choroidal Vascular Loss in Clinically Documented Cases of Age-Related Macular Degeneration.

ABSTRACT: Age-related macular degeneration (AMD) is a multifactorial disease with genetic and environmental factors contributing to risk. Histopathologic changes underlying AMD are not fully understood, particularly the relationship between choriocapillaris (CC) dysfunction and phenotypic variability of this disease.To examine histopathologic changes in the CC of eyes with clinically documented AMD.The study was designed in 2011. Tissues were collected post mortem (2012-2016), and histopathological images were obtained from participants enrolled in AMD studies since 1988. Clinical records and images were collected from participants as standard protocol. Eyes without AMD (n?=?4) and eyes with early (n?=?9), intermediate (n?=?5), and advanced stages of AMD (geographic atrophy, n?=?5; neovascular disease, n?=?13) were evaluated. Choroidal vasculature was labeled using Ulex europaeus agglutinin lectin and examined using confocal microscopy.A standardized classification system was applied to determine AMD stage. Ocular records and images were reviewed and histopathologic analyses performed. Viability of the choroidal vasculature was analyzed for each AMD stage.All participants were white. Fourteen were male, and 16 were female. The mean age was 90.5 years among AMD patients and 88.5 years among control participants. Submacular CC dropout without retinal pigment eipthelial (RPE) loss was observed in all cases with early stages of AMD. Higher vascular area loss for each AMD stage was observed compared with control participants: 20.5% in early AMD (95% CI, 11.2%-40.2%; P?

SUBMITTER: Seddon JM

PROVIDER: S-EPMC6014730 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Histopathological Insights Into Choroidal Vascular Loss in Clinically Documented Cases of Age-Related Macular Degeneration.

Seddon Johanna M JM McLeod D Scott DS Bhutto Imran A IA Villalonga Mercedes B MB Silver Rachel E RE Wenick Adam S AS Edwards Malia M MM Lutty Gerard A GA

JAMA ophthalmology 20161101 11

<h4>Importance</h4>Age-related macular degeneration (AMD) is a multifactorial disease with genetic and environmental factors contributing to risk. Histopathologic changes underlying AMD are not fully understood, particularly the relationship between choriocapillaris (CC) dysfunction and phenotypic variability of this disease.<h4>Objective</h4>To examine histopathologic changes in the CC of eyes with clinically documented AMD.<h4>Design, setting, and participants</h4>The study was designed in 201 ...[more]

PMID: 27657855

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Project description:Age-related macular degeneration (AMD) is a major cause of blindness in developed countries. The molecular pathogenesis of early events in AMD is poorly understood. We investigated differential gene expression in samples of human retinal pigment epithelium (RPE) and choroid from early AMD and control maculas with exon-based arrays.Gene expression levels in nine human donor eyes with early AMD and nine control human donor eyes were assessed using Affymetrix Human Exon ST 1.0 arrays. Two controls did not pass quality control and were removed. Differentially expressed genes were annotated using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and gene set enrichment analysis (GSEA) was performed on RPE-specific and endothelium-associated gene sets. The complement factor H (CFH) genotype was also assessed, and differential expression was analyzed regarding high AMD risk (YH/HH) and low AMD risk (YY) genotypes.Seventy-five genes were identified as differentially expressed (raw p value <0.01; ?50% fold change, mean log2 expression level in AMD or control ? median of all average gene expression values); however, no genes were significant (adj. p value <0.01) after correction for multiple hypothesis testing. Of 52 genes with decreased expression in AMD (fold change <0.5; raw p value <0.01), 18 genes were identified by DAVID analysis as associated with vision or neurologic processes. The GSEA of the RPE-associated and endothelium-associated genes revealed a significant decrease in genes typically expressed by endothelial cells in the early AMD group compared to controls, consistent with previous histologic and proteomic studies. Analysis of the CFH genotype indicated decreased expression of ADAMTS9 in eyes with high-risk genotypes (fold change = -2.61; raw p value=0.0008).GSEA results suggest that RPE transcripts are preserved or elevated in early AMD, concomitant with loss of endothelial cell marker expression. These results are consistent with the notion that choroidal endothelial cell dropout or dedifferentiation occurs early in the pathogenesis of AMD.

Project description:BackgroundTo investigate the characteristics of retinal vessels and retinal thickness in eyes with early age-related macular degeneration (AMD) with or without reticular pseudodrusen.MethodsWe retrospectively evaluated the clinical history and optical coherence tomography (OCT) and OCT angiography images of consecutive patients with early AMD. We calculated the retinal vessel densities of the superficial and deep capillary plexus with the ImageJ software (National Institutes of Health, Bethesda, MD, USA) and investigated the relationship with mean retinal thickness and subfoveal choroidal thickness.ResultsWe included 135 early AMD eyes and classified 60 of them into a reticular pseudodrusen group and 75 into a non-reticular pseudodrusen group. The vascular densities of the superficial and deep capillary plexus in the reticular pseudodrusen group (32.35% ± 3.67 and 26.71% ± 2.88%) were not different from those of the non-reticular pseudodrusen group (33.18% ± 2.2% and % 27.43 ± 1.79%; P = 0.546 and P = 0.318, respectively). The retinal thickness of the reticular pseudodrusen group (287.31 μm ± 24.36 μm) did not differ from that of the non-reticular pseudodrusen group (294.27 μm ± 20.71 μm; P = 0.493), while subfoveal choroidal thickness in the reticular pseudodrusen group (158.13 μm ± 42.53 μm) was lower than that in the non-reticular pseudodrusen group (237.89 μm ± 60.94 μm; P < 0.001). Multivariate analysis revealed that lower vascular density of the superficial capillary plexus and subfoveal choroidal thickness were associated with retinal thinning in reticular pseudodrusen group (P = 0.003 and P = 0.036) and older age was associated with retinal thickness in the non-reticular pseudodrusen group (P = 0.005).ConclusionsRetinal thinning in early AMD patients with reticular pseudodrusen was accompanied by choroidal and retinal vascular loss, which suggests a possible linkage of retinal thinning with vascular alterations.

Dataset Information

Histopathological Insights Into Choroidal Vascular Loss in Clinically Documented Cases of Age-Related Macular Degeneration.

Publications

Histopathological Insights Into Choroidal Vascular Loss in Clinically Documented Cases of Age-Related Macular Degeneration.

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