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arXiv · 2605.30463

Meta-analysis of scRNA-seq data for choroidal endothelial cells in dry Age-related Macular Degeneration

Kyle M. Veksler·Levi Dong·Timothy A. Blenkinsop·Aurelian Radu
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Abstract

The mechanisms that lead to dry Age-related Macular Degeneration are largely unelucidated, which prevents the introduction of effective therapies. Experimental support exists in the literature for the hypothesis that choroidal endothelial cell (ChEC) dysfunction precedes the loss of macular retinal pigmented epithelial (RPE), which may be only a secondary consequence of inadequate blood supply. If so, interventions at the level of ChEC could constitute an under investigated therapeutic strategy. Datasets regarding the transcriptional changes in early or intermediate dry AMD are publicly available, but for some some of them the information about ChECs have not been analyzed, or not analyzed using the most powerful and recent software tools. We present here new data generated by our bioinformatics analysis of these datasets. The main new finding is that angiogenesis is initiated in dry AMD, as it is in wet AMD. However, contrary to wet AMD, in dry AMD angiogenesis fails to execute, and therefore the blood supply that supports the RPE becomes gradually insufficient, leading to their dysfunctionality and death. The data support a unitary hypothesis of the origin / initiation / etiology of both dry and wet AMD, namely that both are initiated by ChEC dysfunction - either insufficient / abortive angiogenesis in dry AMD, or excessive angiogenesis in wet AMD. Pathway analysis also reveals as perturbed Notch and TNF signaling, endothelial to mesenchymal transition (EndoMT), mitochondria, "fluid shear stress", "osteoclast differentiation" and "calcification/osteoporosis". Overall, the new data provide a rationale for experimental studies, to validate and further characterize these perturbations, and investigate strategies to correct them.

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Kyle M. Veksler, Levi Dong, Timothy A. Blenkinsop, Aurelian Radu. 2026-05-28. Meta-analysis of scRNA-seq data for choroidal endothelial cells in dry Age-related Macular Degeneration. https://arxiv.org/abs/2605.30463

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