AI Article Synopsis
- Macular neovascularization is a serious complication of age-related macular degeneration, linked to abnormal blood vessel growth in the eye, and researchers seek to understand how various cell types are affected.
- The study utilized spatial RNA sequencing on both affected and healthy human donor eyes to identify genes associated with macular neovascularization and discern which cell types exhibited altered gene expression.
- Key findings revealed increased expression of certain signaling genes in endothelial cells and identified potential regulatory factors like VEGF and TGFB1, contributing to our understanding of the pathological changes in macular neovascularization.
Article Abstract
Purpose: Macular neovascularization is a relatively common and potentially visually devastating complication of age-related macular degeneration. In macular neovascularization, pathologic angiogenesis can originate from either the choroid or the retina, but we have limited understanding of how different cell types become dysregulated in this dynamic process.
Methods: To study how gene expression is altered in focal areas of pathology, we performed spatial RNA sequencing on a human donor eye with macular neovascularization as well as a healthy control donor. We performed differential expression to identify genes enriched within the area of macular neovascularization and used deconvolution algorithms to predict the originating cell type of these dysregulated genes.
Results: Within the area of neovascularization, endothelial cells demonstrated increased expression of genes related to Rho family GTPase signaling and integrin signaling. Likewise, VEGF and TGFB1 were identified as potential upstream regulators that could drive the observed gene expression changes produced by endothelial and retinal pigment epithelium cells in the macular neovascularization donor. These spatial gene expression profiles were compared to previous single-cell gene expression experiments in human age-related macular degeneration as well as a model of laser-induced neovascularization in mice. As a secondary aim, we investigated regional gene expression patterns within the macular neural retina and between the macular and peripheral choroid.
Conclusions: Overall, this study spatially analyzes gene expression across the retina, retinal pigment epithelium, and choroid in health and describes a set of candidate molecules that become dysregulated in macular neovascularization.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615143 | PMC |
| http://dx.doi.org/10.1167/iovs.64.13.40 | DOI Listing |
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