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Translaminar Autonomous System Model for the Modulation of Intraocular and Intracranial Pressure in Human Donor Posterior Segments
Published on: April 24, 2020
Cochlin, intraocular pressure regulation and mechanosensing
Manik Goel1, Adam E Sienkiewicz, Renata Picciani
1Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States of America.
Plos One
|April 13, 2012
Summary
Cochlin, an extracellular matrix protein, regulates intraocular pressure (IOP). Increased cochlin levels raise IOP, while reduced levels decrease it, suggesting a role in mechanosensing fluid shear stress.
Area of Science:
- Biochemistry
- Ophthalmology
- Mechanobiology
Background:
- Fluid shear stress influences biological functions.
- Mechanisms of shear mechanosensing in the extracellular matrix (ECM) and its transduction into cytoskeletal changes are not fully understood.
- Cochlin is an ECM protein with an uncharacterized function.
Purpose of the Study:
- To investigate the function of cochlin in the regulation of intraocular pressure (IOP).
- To explore the potential role of cochlin in mechanosensing fluid shear stress.
Main Methods:
- Overexpression and downregulation of cochlin in mouse models (DBA/2J-Gpnmb(+)/SjJ and DBA/2J mice) using lentiviral vectors and targeted gene disruption.
- Reintroduction and injection of exogenous cochlin.
- Assessment of cochlin multimerization in response to varying perfusion rates.
- Analysis of cochlin proteolysis by trypsin and proteinase K.
Main Results:
- Overexpression of cochlin increased IOP; downregulation decreased IOP.
- Reintroduction of cochlin into cochlin-null mice elevated IOP.
- Exogenous cochlin administration also increased IOP.
- Increased perfusion rates led to cochlin multimerization, reducing its proteolysis.
Conclusions:
- Cochlin plays a significant role in regulating intraocular pressure (IOP) in DBA/2J mice.
- Cochlin's shear-induced multimerization suggests a potential mechanosensing capability.
- Cochlin may regulate IOP through mechanosensing of shear stress in the ECM.
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