Related Experiment Video
Updated: Jul 3, 2026
13:47
Laser Capture Microdissection of Highly Pure Trabecular Meshwork from Mouse Eyes for Gene Expression Analysis
Published on: June 3, 2018
Mitochondrial defects and dysfunction in calcium regulation in glaucomatous trabecular meshwork cells
Yuan He1, Jian Ge, Joyce Tombran-Tink
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Investigative Ophthalmology & Visual Science
|July 11, 2008
Summary
Primary open-angle glaucoma (POAG) trabecular meshwork cells exhibit impaired calcium regulation and mitochondrial dysfunction, increasing vulnerability to calcium stress. These cellular defects may contribute to elevated intraocular pressure (IOP) in POAG.
Area of Science:
- Ophthalmology
- Cell Biology
- Mitochondrial Biology
Background:
- Intracellular calcium ion (Ca(2+)) homeostasis is critical for cellular function.
- Disrupted Ca(2+) homeostasis and subsequent mitochondrial dysfunction contribute to various pathologies.
- Trabecular meshwork (TM) cells play a key role in regulating intraocular pressure (IOP).
Purpose of the Study:
- To investigate intracellular Ca(2+) levels and mitochondrial vulnerability to Ca(2+) stress in TM cells from individuals with primary open-angle glaucoma (POAG).
- To understand the role of mitochondrial dysfunction in POAG pathogenesis.
Main Methods:
- Primary cultures of TM cells from POAG (GTM) and non-diseased (NTM) eyes were utilized.
- Cells were treated with various calcium regulators, mitochondrial inhibitors, and chelators.
- Intracellular and mitochondrial Ca(2+) concentrations, mitochondrial membrane potential (DeltaPsim), and cyclophilin D expression were measured.
Main Results:
- POAG TM cells demonstrated increased intracellular and mitochondrial Ca(2+) concentrations, enhanced mitochondrial calcium-induced calcium release (mCICR), and increased mitochondrial permeability transition pore (MPTP) opening compared to controls.
- POAG TM cells exhibited decreased mitochondrial membrane potential (DeltaPsim) and elevated cyclophilin D expression.
- Chelation of intracellular Ca(2+), inhibition of IP3R, and MPTP opening suppressed mitochondrial dysfunction.
Conclusions:
- TM cells in POAG exhibit defective mitochondrial function, rendering them abnormally vulnerable to Ca(2+) stress.
- Dysfunctional calcium regulation in TM cells may contribute to the failure in controlling IOP in POAG.
- Pharmacologic targeting of IP3R, MPTP opening, and cyclophilin D presents potential therapeutic strategies for POAG.
Related Concept Videos
01:25Glaucoma: Overview
Glaucoma is an eye condition characterized by increased intraocular pressure that damages the retina and optic nerve, leading to irreversible blindness if left untreated. The human eye has various components, including the cornea, iris, pupil, lens, and optic nerve. Aqueous humor is secreted by the epithelium of the ciliary body in the posterior chamber and flows through the trabecular meshwork and canal of Schlemm, maintaining normal intraocular pressure. The trabecular meshwork and the canal...
01:45Mitochondrial Membranes
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
01:28The Inner Mitochondrial Membrane
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...