Genetic and pharmacological correction of impaired mitophagy in retinal ganglion cells rescues glaucomatous neurodegeneration.

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Tác giả: J Cameron Millar, Abbot F Clark, Balasankara Reddy Kaipa, Ramesh B Kasetti, Karthikeyan Kesavan, Bindu Kodati, Prabhavathi Maddineni, Sam Yacoub, Gulab S Zode

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : bioRxiv : the preprint server for biology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 674064

Progressive loss of retinal ganglion cells (RGCs) and degeneration of optic nerve axons are the pathological hallmarks of glaucoma. Ocular hypertension (OHT) and mitochondrial dysfunction are linked to neurodegeneration and vision loss in glaucoma. However, the exact mechanism of mitochondrial dysfunction leading to glaucomatous neurodegeneration is poorly understood. Using multiple mouse models of OHT and human eyes from normal and glaucoma donors, we show that OHT induces impaired mitophagy in RGCs, resulting in the accumulation of dysfunctional mitochondria and contributing to glaucomatous neurodegeneration. Using mitophagy reporter mice, we show that impaired mitophagy precedes glaucomatous neurodegeneration. Notably, the pharmacological rescue of impaired mitophagy via Torin-2 or genetic upregulation of RGC-specific Parkin expression restores the structural and functional integrity of RGCs and their axons in mouse models of glaucoma and
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