Primary open-angle glaucoma (POAG) is a genetically, physiologically, and phenotypically complex neurodegenerative disorder. This study addressed the expanding collection of genes associated with POAG, referred to as the “POAGome.” We used bioinformatics tools to perform an extensive, systematic literature search and compiled 542 genes with confirmed associations with POAG and its related phenotypes (normal tension glaucoma, ocular hypertension, juvenile open-angle glaucoma, and primary congenital glaucoma). The genes were classified according to their associated ocular tissues and phenotypes, and functional annotation and pathway analyses were subsequently performed. Our study reveals that no single molecular pathway can encompass the pathophysiology of POAG. The analyses suggested that inflammation and senescence may play pivotal roles in both the development and perpetuation of the retinal ganglion cell degeneration seen in POAG. The TGF-β signaling pathway was repeatedly implicated in our analyses, suggesting that it may be an important contributor to the manifestation of POAG in the anterior and posterior segments of the globe. We propose a molecular model of POAG revolving around TGF-β signaling, which incorporates the roles of inflammation and senescence in this disease. Finally, we highlight emerging molecular therapies that show promise for treating POAG.

Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Male C57BL/6J mice were randomized into groups receiving IV iron-sucrose (+Fe) or 30% sucrose (−Fe). Iron levels in neurosensory retina (NSR), retinal pigment epithelium (RPE), and choroid were assessed using immunofluorescence, quantitative PCR, and the Perls’ iron stain. Iron levels were most increased in the RPE and choroid while levels in the NSR did not differ significantly in +Fe mice compared to controls. Eyes from +Fe mice shared histological features with AMD, including Bruch’s membrane (BrM) thickening with complement C3 deposition, as well as RPE hypertrophy and vacuolization. This focal degeneration correlated with areas with high choroidal iron levels. Ultrastructural analysis provided further detail of the RPE/photoreceptor outer segment vacuolization and Bruch’s membrane thickening. Findings were correlated with a clinical case of a 43-year-old patient who developed numerous retinal drusen, the hallmark of AMD, within 11 months of IV iron therapy. Our results suggest that IV iron therapy may have the potential to induce or exacerbate a form of retinal degeneration. This retinal degeneration shares features with AMD, indicating the need for further study of AMD risk in patients receiving IV iron treatment.

This article investigates the three-dimensional self-assembly of submillimeter scale polyhedra using surface forces. Using a combination of energy landscape calculations and experiments, we investigate the influence of patterns of hydrophobic surfaces on generating defect-free, closed-packed aggregates of polyhedra, with a focus on cubic units. Calculations show that surface patterning strongly affects the interaction between individual units as well as that of the unit with the growing assembly. As expected, an increase in the hydrophobic surface area on each face results in larger global minima. However, it is the distribution of hydrophobic surface area on each cubic face that is strongly correlated to the energetic parameters driving low-defect assembly. For patterns with the same overall area, minimizing the radius of gyration and maximizing the angular distribution leads to steep energy curves, with a lower propensity for entrapment in metastable states. Experimentally, 200-500 microm sized metallic polyhedra were fabricated using a self-folding process, and the exposed surfaces were coated with a hydrophobic polymer. Cubes with surface patterns were agitated to cause aggregative self-assembly. Experimental results were consistent with energy calculations and suggest that geometric patterns with large overall areas, low radii of gyration, and high angular distributions result in efficient and low-defect assembly.