Single-cell analysis reveals inflammatory interactions driving macular degeneration.

Due to commonalities in pathophysiology, age-related macular degeneration (AMD) represents a uniquely accessible model to investigate therapies for neurodegenerative diseases, leading us to examine whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 11 postmortem human retinas with age-related macular degeneration and 6 control retinas with no history of retinal disease. We create a machine-learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer's disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1ß which drives angiogenesis characteristic of disease pathogenesis. We validated this mechanism using in vitro and in vivo assays in mouse, identifying a possible new therapeutic target for AMD and possibly other neurodegenerative conditions. Thus, due to shared glial states, the retina provides a potential system for investigating therapeutic approaches in neurodegenerative diseases.

Herbal Medicines in Glaucoma Treatment.

Glaucoma is the leading cause of irreversible blindness worldwide. Optimizing treatment is important to protecting vision. The current standard of therapy for glaucoma involves lowering the intraocular pressure (IOP) through medical, laser, and/or surgical therapy. Nevertheless, there are an increasing number of glaucoma patients that use alternative medicines to treat their glaucoma or supplement their traditional glaucoma management. Ginkgo biloba, bilberry, and medical marijuana are amongst the most commonly used medicinal plants by glaucoma patients. We reviewed the literature to determine the benefits, safety, and efficacy of these herbal remedies. Though ginkgo biloba and bilberry may prevent or slow down retinal ganglion cell death, there is no evidence yet to suggest that they alter the course of glaucoma. Medical marijuana has shown IOP lowering effect in some individuals, but its short duration of action, significant adverse effects, and addictive potential have rendered it an inappropriate standard therapeutic agent for glaucoma. Larger studies with longer durations that investigate the effect of herbal medicines on the course of glaucoma in comparison to the current standard of care are needed to elucidate their benefits in glaucoma treatment.

Polyester vascular patches acquire arterial or venous identity depending on their environment.

Polyester is commonly used in vascular surgery for patch angioplasty and grafts. We hypothesized that polyester patches heal by infiltration of arterial or venous progenitor cells depending on the site of implantation. Polyester patches were implanted into the Wistar rat aorta or inferior vena cava and explanted on day 7 or 30. Neointima that formed on polyester patches was thicker in the venous environment compared to the amount that formed on patches in the arterial environment. Venous patches had more cell proliferation and greater numbers of VCAM-positive and CD68-positive cells, whereas arterial patches had greater numbers of vimentin-positive and alpha-actin-positive cells. Although there were similar numbers of endothelial progenitor cells in the neointimal endothelium, cells in the arterial patch were Ephrin-B2- and notch-4-positive while those in the venous patch were Eph-B4- and COUP-TFII-positive. Venous patches treated with an arteriovenous fistula had decreased neointimal thickness; neointimal endothelial cells expressed Ephrin-B2 and notch-4 in addition to Eph-B4 and COUP-TFII. Polyester patches in the venous environment acquire venous identity, whereas patches in the arterial environment acquire arterial identity; patches in the fistula environment acquire dual arterial-venous identity. These data suggest that synthetic patches heal by acquisition of identity of their environment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3422-3431, 2017.