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Updated: Sep 15, 2025

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
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Secretion of transthyretin: molecular mechanisms dependent on the endoplasmic reticulum

Jia Meng1, Shan-Jun Cai1,2,3,4

  • 1Department of Ophthalmology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

Frontiers in Physiology
|July 16, 2025
PubMed

Hereditary transthyretin amyloidosis (ATTRv) results from genetic mutations that destabilize transthyretin (TTR), leading to the formation of extracellular aggregates and amyloid fibrils. A common pathological feature of ATTRv is the capacity of TTR variants to evade endoplasmic reticulum quality control (ERQC) and be secreted, underscoring the critical role of ER regulation in disease pathogenesis. Notably, the TTR Gly83Arg mutation causes familial vitreous amyloidosis, a subtype distinguished by abnormal TTR deposition in the ocular vitreous cavity. Current therapies for ATTRv are ineffective in crossing the blood-retinal barrier or in halting the progression of ocular amyloidosis. This review summarizes the molecular mechanisms of ER-regulated TTR secretion and explores potential causes of ocular amyloid deposition, aiming to provide mechanistic insights into familial vitreous amyloidosis.

Keywords:
endoplasmic reticulumendoplasmic reticulum quality controltransthyretinunfolded protein responsevitreous amyloidosis

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