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EMBO Reports Jul 2023Dysregulation of the activity of the mechanistic target of rapamycin complex 1 (mTORC1) is commonly linked to aging, cancer, and genetic disorders such as tuberous...
Dysregulation of the activity of the mechanistic target of rapamycin complex 1 (mTORC1) is commonly linked to aging, cancer, and genetic disorders such as tuberous sclerosis (TS), a rare neurodevelopmental multisystemic disease characterized by benign tumors, seizures, and intellectual disability. Although patches of white hair on the scalp (poliosis) are considered as early signs of TS, the underlying molecular mechanisms and potential involvement of mTORC1 in hair depigmentation remain unclear. Here, we have used healthy, organ-cultured human scalp hair follicles (HFs) to interrogate the role of mTORC1 in a prototypic human (mini-)organ. Gray/white HFs exhibit high mTORC1 activity, while mTORC1 inhibition by rapamycin stimulated HF growth and pigmentation, even in gray/white HFs that still contained some surviving melanocytes. Mechanistically, this occurred via increased intrafollicular production of the melanotropic hormone, α-MSH. In contrast, knockdown of intrafollicular TSC2, a negative regulator of mTORC1, significantly reduced HF pigmentation. Our findings introduce mTORC1 activity as an important negative regulator of human HF growth and pigmentation and suggest that pharmacological mTORC1 inhibition could become a novel strategy in the management of hair loss and depigmentation disorders.
Topics: Humans; Hair Follicle; Mechanistic Target of Rapamycin Complex 1; Pigmentation; Melanocytes; Hair Color
PubMed: 37212043
DOI: 10.15252/embr.202256574 -
Journal of Vitreoretinal Diseases 2023To present a case of retinal vascular disease characterized primarily by capillary nonperfusion in an adult with Coats plus syndrome (CPS). : A case and its findings...
To present a case of retinal vascular disease characterized primarily by capillary nonperfusion in an adult with Coats plus syndrome (CPS). : A case and its findings were analyzed. : A 38-year-old woman with a history of poliosis, thrombocytopenia, seizures, and white-matter brain lesions was referred for evaluation of bilateral blurred central vision. Fluorescein angiography showed extensive bilateral retinal capillary nonperfusion with retinal arteriolitis in the right eye. Genetic testing found 2 pathological mutations in the conserved telomere maintenance component 1 () gene, diagnostic of CPS. : Genetic testing may be diagnostic in patients who present with retinal vascular disease and systemic disease suggestive of CPS.
PubMed: 37974921
DOI: 10.1177/24741264231171465 -
Prognosis in patients with alopecia areata with poliosis: A retrospective cohort study of 479 cases.Indian Journal of Dermatology,... 2023
Topics: Humans; Alopecia Areata; Retrospective Studies; Pigmentation Disorders; Hair Diseases; Prognosis
PubMed: 37067136
DOI: 10.25259/IJDVL_552_2022 -
Annals of Dermatology Feb 2024
PubMed: 38325435
DOI: 10.5021/ad.22.171 -
JAAD Case Reports Aug 2023
PubMed: 37521192
DOI: 10.1016/j.jdcr.2023.06.018 -
Case Reports in Oncology 2024Ipilimumab and nivolumab are checkpoint inhibitors that are known to cause a multitude of inflammatory ocular adverse events. Here we report a patient with poliosis and...
INTRODUCTION
Ipilimumab and nivolumab are checkpoint inhibitors that are known to cause a multitude of inflammatory ocular adverse events. Here we report a patient with poliosis and symptomatic depigmentation of the choroid and retinal pigment epithelium (RPE) associated with checkpoint inhibitor therapy for cutaneous melanoma.
CASE PRESENTATION
The patient presented with floaters in both eyes and concerns for intraocular metastases of metastatic cutaneous melanoma after 1 month of therapy with ipilimumab and nivolumab. External examination revealed poliosis of her eyebrows and eyelashes. Fundus photography demonstrated multiple 1-3 disc-diameter hypopigmented placoid flat areas in the RPE/choroid exposing underlying choroidal vessels in both eyes. At subsequent evaluation 7 months later (after an additional 6 months of checkpoint inhibitor therapy), the lesions appeared more blanched. Evaluation nearly 20 months after the initial presentation showed no significant changes from her prior visit despite cessation of checkpoint inhibitor therapy for 13 months.
CONCLUSION
Checkpoint inhibitor therapy for cutaneous melanoma metastases can cause depigmentation of the choroid and RPE that must be differentiated from progression of intraocular melanoma.
PubMed: 38264011
DOI: 10.1159/000535745