Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1. ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein (HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells (RGCs) by using an artificial intelligence (AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing (scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1-/- retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1-/- mice using atorvastatin reduced the cholesterol level in the retina, thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1-/- retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression.

Plant communities in mountainous areas shift gradually as climatic conditions change with altitude. How trait structure in multivariate space adapts to these varying climates in natural forest stands is unclear. Studying the multivariate functional trait structure and redundancy of tree communities along altitude gradients is crucial to understanding how temperature change affects natural forest stands. In this study, the leaf area, specific leaf area, leaf carbon, nitrogen, and phosphorous content from 1,590 trees were collected and used to construct the functional trait space of 12 plant communities at altitudes ranging from 800 m to 3,800 m across three mountains. Hypervolume overlap was calculated to quantify species trait redundancy per community. First, hypervolumes of species exclusion and full species set were calculated, respectively. Second, the overlap between these two volumes was calculated to obtain hypervolume overlap. Results showed that the functional trait space significantly increased with mean annual temperature toward lower altitudes within and across three mountains, whereas species trait redundancy had different patterns between mountains. Thus, warming can widen functional trait space and alter the redundancy in plant communities. The inconsistent patterns of redundancy between mountains suggest that warming exerts varying influences on different ecosystems. Identification of climate-vulnerable ecosystems is important in the face of global warming.