Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced by neighboring epithelial cells, the retinal pigment epithelium (RPE) and podocytes, respectively. Dysregulation of RPE- and podocyte-derived VEGF is associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, and glomerular thrombotic microangiopathy (TMA). Since complement activation and genetic variants in inhibitory complement factor H (CFH) are also features of both ARMD and TMA, we hypothesized that VEGF and CFH interact. Here, we demonstrated that VEGF inhibition decreases local CFH and other complement regulators in the eye and kidney through reduced VEGFR2/PKC-α/CREB signaling. Patient podocytes and RPE cells carrying disease-associated CFH genetic variants had more alternative complement pathway deposits than controls. These deposits were increased by VEGF antagonism, a common wet ARMD treatment, suggesting that VEGF inhibition could reduce cellular complement regulatory capacity. VEGF antagonism also increased markers of endothelial cell activation, which was partially reduced by genetic complement inhibition. Together, these results suggest that VEGF protects the retinal and glomerular microvasculature, not only through VEGFR2-mediated vasculotrophism, but also through modulation of local complement proteins that could protect against complement-mediated damage. Though further study is warranted, these findings could be relevant for patients receiving VEGF antagonists.

Human brain imaging identifies the posterior cingulate cortex (PCC) as an anatomically and physiologically unique brain region. Structurally, the PCC has been reported as a central network hub of neocortical connectivity. Physiologically, the PCC regularly displays one of the highest metabolic rates in neocortex. However, despite these striking features, the function of PCC remains poorly understood. While the PCC is typically viewed as a key node of the default network (DN), owing to its suppressed activity during many attention demanding tasks, there’s little consensus regarding the contribution of PCC to behavior. For example, while human neuroimaging data suggest a role of PCC in episodic memory retrieval ‐ one of just a few tasks that increase PCC activity ‐ this view is inconsistent with non‐human primate physiology, which suggests a role of PCC in cognitive control. Central to this confusion is the varied and inconsistent anatomy/nomenclature used to define PCC. Across human studies, the term “PCC” is often used interchangeably with “precuneus” and/or “retrosplenial cortex”. It is therefore clear that a key requisite for progress in understanding PCC function is establishing reliable anatomical landmarks and associated nomenclature. From this foundation, the functional neuroanatomy of PCC can be built. With this goal in mind, we report on a systematic investigation of the macroanatomical features of the posteromedial cortex (PMC), which includes the posterior cingulate, precuneal, and retrosplenial cortices. Focusing chiefly on sulcal organization, we reliability identified several well‐known landmarks (i.e. marginal ramus of the cingulate sulcus (mcgs), parieto‐occipital sulcus, sub‐parietal sulcus, etc.). We also observed a high variability of other less studied sulci, such as those comprising the precuneal sulcal complex. However, we also identified a new reliable sulcus located inferior to the mcgs, which we term the inframarginal sulcus (ifrms). Interestingly, subsequent analyses of anatomical properties revealed the ifrms to display a unique profile of myelination, thickness, and cytoarchitecture. In addition, functional data also converged on the ifrms to highlight that this region, reflecting the dorsal aspect of the PCC, co‐localizes to the well known cognitive control network (CCN). Together, this tripartite convergence of macroanatomical, microanatomical, and functional properties suggests the ifrms to be a reliable and unique landmark within the PCC. This observation not only serves as a new landmark of PCC functional neuroanatomy, but also may help reconcile prior discrepancies between human and non‐human studies. This clarification points to PCC, particularly its dorsal aspect, as more engaged by cognitive control processes (i.e. CCN), as distinct from ventral PCC regions, being more engaged by memory retrieval processes (i.e. DN). Finally, the fact that a sulcus, which identifies multiple anatomical and functional cortical features, has remained un‐identified is striking considering neuroana...