Signalling by senescent melanocytes hyperactivates hair growth.

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

Peripheral retinal neovascularization in talc retinopathy.

BACKGROUND: Neovascularization of the peripheral retina can be present in a number of systemic and ocular diseases. Very rarely, peripheral retinal neovascularization can also be manifested in intravenous drug abusers. In addition to ocular complications, intravenous drug abusers are at high risk for contracting various infections and the development of pulmonary and cardiovascular diseases. We present a case of a chronic heroin and cocaine abuser with bilateral peripheral retinal neovascularization, pulmonary complications, and a history of endocarditis. CASE REPORT: A patient with a 20-year history of heroin and cocaine abuse initially presented for a routine eye examination. Fundus examination revealed pinpoint white deposits centered in both maculas, engorged vascular fronds with a patch of intraretinal hemorrhage in the peripheral retinal of the right eye and neovascularization of the disc as well as exudation with adjacent focal preretinal hemorrhage in the left eye. The patient underwent fluorescein angiography and was screened for diabetes, sarcoidosis, and sickle cell disease. When no systemic disease could be discovered, it was concluded that the peripheral retinal neovascularization developed as a result of vascular occlusion from heroin and cocaine abuse. DISCUSSION: It is important to investigate the cause of neovascularization in the peripheral retina. Retinal vascular emboli such as talc are common in drug abusers, but in most cases, the retinal deposits pose only a minimal threat to vision. However, this case shows that careful retinal examination is warranted in drug abusers to rule out neovascularization of the retina. Other causes of peripheral retinal neovascularization should be ruled out as well. These conditions include sickle cell retinopathy, sarcoidosis, diabetic retinopathy, blood dyscrasias, retinal vascular occlusion, Eales' disease, and other systemic conditions, so that appropriate ocular and systemic treatment can be provided. Peripheral retinal neovascularization is best treated by pan-retinal photocoagulation.