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Sanjoy K. Bhattacharya, Katyayini Aribindi, Manik Goel, Richard K. Lee; Endogenous Lipids as Regulators of Intraocular Pressure in Glaucoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3829.
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To determine whether differentially present phosphoserines in the normal compared to glaucomatous aqueous humor modulate intraocular pressure (IOP) and mechanotransduction channels on the trabecular meshwork (TM) cells.
All studies were performed adhering to the ARVO Statement for the Use of Animals in Research and to the tenets of declaration of Helsinki. Differential mass spectrometric shotgun lipidomic analyses were performed with normal and glaucomatous aqueous humor (n= 10 each) for Phosphatidylserine species and the corresponding lysophospholipids with neutral loss scan for m/z 87.1 (serine residue) using a TSQ Quantum Access Max instrument. Intracameral injection of selected identified lipids in DBA/2J mice (n=42-48) was made using ultramicropump II. IOP measurements in control and experimental mice were carried out using the Tonolab and intraocular cannulation. Eyes were enucleated and optic nerve damage was assessed using paraphenylenediamine (PPD) staining. Primary human TM cells were subjected to treatment with lipids. Mechanotransduction channels (TREK-1, Piezo 1 &2) found in the TM by genomic analyses were subjected to determination of level changes by Western Blot analyses.
We identified differential downregulation of a phosphoserine (lipid L525) in the glaucomatous aqueous humor. Intracameral injection of Lipid Z (a phosphoserine) in the TM of DBA/2J starting at 5 months of age (n=42-48) resulted in dramatic reduction (about 6 mm of Hg) in peak IOP over uninjected control mice. The optic nerve damage in DBA/2J mice correlated with elevated IOP. Administration of phosphoserine renders level changes in Piezo1 and Piezo 2 channels determined by Western Blot analyses in DBA/2J mice and in primary human TM cells.
The level of IOP is regulated by select endogenous phosphoserines. The present investigation suggests endogenous phosphoserines may be involved in the regulation of IOP mediated through mechanotransduction channels.
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