Mechanosensitive Channel MscL for Glaucoma IOP Reduction

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Solution Overview

Problem

Current treatments for glaucoma, including pharmacological and surgical methods, have significant limitations such as systemic side effects, patient non-compliance, and inconsistent outcomes, necessitating the development of a safe and effective long-lasting therapeutic solution to lower intraocular pressure.

Innovation Solution

The use of heterologously expressed mechanosensitive channels, specifically the mechanosensitive channel of large conductance (MscL), as a transgenic pressure modulator to sense and modulate pressure changes in trabecular meshwork cells, facilitating increased outflow of aqueous humor and reducing intraocular pressure through viral or non-viral delivery methods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stress or pressure

If pharmacological treatments are used to lower intraocular pressure, then IOP reduction is achieved, but systemic side effects occur

Engineering Contradiction:

Improveintraocular pressureVSAvoidsystemic side effects

Core Design Contradiction:

Stress or pressureVSObject-affected harmful factors

Solution Approach 1:

The patent uses mechanosensitive channels (MscL, MscS, Piezo) as intermediary proteins that directly sense and respond to intraocular pressure changes, converting mechanical pressure signals into channel opening events that facilitate aqueous humor outflow, thereby bypassing the need for pharmacological intermediaries that cause systemic side effects

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces pharmacological chemical systems with a mechanical sensing system where mechanosensitive channels directly detect pressure changes through membrane tension and activate accordingly, substituting chemical drug action with a purely mechanical transduction mechanism that avoids systemic pharmacological effects

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Productivity

If surgical methods are used to improve aqueous humor outflow, then drainage is enhanced, but patient compliance and consistency issues arise

Engineering Contradiction:

Improveaqueous humor outflowVSAvoidtreatment consistency

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent implements a self-regulating system where mechanosensitive channels automatically sense intraocular pressure and activate to facilitate aqueous humor outflow without requiring external control or patient intervention, ensuring consistent treatment效果 that does not depend on patient compliance

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The patent creates a feedback loop where mechanosensitive channels continuously monitor intraocular pressure levels and dynamically adjust their opening state in response to pressure changes, maintaining homeostatic control of aqueous humor outflow that adapts to varying physiological conditions

Inventive Principle:

Principle #23Feedback

3Stress or pressure

If current glaucoma treatments are used, then IOP reduction is achieved, but long-lasting therapeutic solution is not provided

Engineering Contradiction:

Improveintraocular pressureVSAvoidtherapeutic duration

Core Design Contradiction:

Stress or pressureVSDuration of action of moving object

Solution Approach 1:

The patent establishes continuous therapeutic action through mechanosensitive channels that remain expressed in trabecular meshwork cells and continuously monitor and respond to pressure changes over time, providing sustained IOP control without the intermittent dosing required by pharmacological treatments

Inventive Principle:

Principle #20Continuity of useful action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach effectively lowers intraocular pressure, potentially providing a long-lasting solution for glaucoma treatment with reduced side effects and improved patient compliance, as demonstrated by successful expression and function of MscL in mammalian cells and reduced IOP in glaucoma models.

Implementation Method 1

The mechanosensitive channel of large conductance (MscL), when expressed in mammalian cells, functions as a tension activated pressure release valve

Methodology Applied

Scientific EffectMechanosensitive channel activation:

Implementation Method 2

MscL directly senses tension in the membrane lipid bilayer of the swelling cell and in response transiently opens its large non-specific pore to release cytoplasmic fluid, thereby relieving the building turgor pressure

Methodology Applied

Scientific EffectPressure-driven transport:

Data Source

PatentUS20230382955A1Method, Compositions and Applications of Mechanosensitive Channels

Publication Date: 2023.11.30 NANOSCOPE TECHNOLOGIES LLC

AI summary

The present invention generally relates to the novel method, compositions and applications of mechanosensitive channels in therapeutics for visual, neurological and other disorders. Specifically, the invention relates to exploitation of mechanosensitive channels' intrinsic property as a transgenic pressure modulator and alternative outflow actuator in the treatment of different diseases such as glaucoma, blood pressure and other diseases involving of cells prone to mechanical or osmotic stress. Furthermore, the invention relates to exploitation of mechanosensitive channels for stimulation of cells enabling therapies for different diseases including pain, as well as molecular delivery to cells triggered by internal and/or external mechanical stimuli.