Ocular Epithelium Tight Junction Permeability Control

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Solution Overview

Problem

Current treatments for ocular pathologies, such as allergic conjunctivitis and dry eye syndrome, fail to effectively regulate paracellular permeability of the ocular surface epithelium, leading to increased penetration of allergens and pathogens, and are often associated with side effects from preservatives like benzalkonium chloride.

Innovation Solution

The use of compounds that modulate cytoskeletal tension in ocular epithelial cells to control the opening and closing of tight junctions, thereby regulating paracellular permeability without de novo protein synthesis or structural degradation, using inhibitors like ML-7 to inhibit myosin light chain kinase and other molecules that affect cytoskeletal contraction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments are used for ocular pathologies, then treatment of allergic conjunctivitis and dry eye syndrome is provided, but paracellular permeability of the ocular surface epithelium is not effectively regulated, leading to increased penetration of allergens and pathogens

Engineering Contradiction:
Improveregulation of paracellular permeabilityVSAvoidpenetration of allergens and pathogens
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the physiological parameter of cytoskeletal tension in ocular epithelial cells by administering compounds that modulate this tension. This parameter change directly regulates tight junction permeability, thereby controlling paracellular permeability and preventing allergen and pathogen penetration while treating ocular pathologies.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The treatment leverages the body's own cytoskeletal mechanisms to regulate tight junctions. By modulating cytoskeletal tension through administered compounds, the ocular epithelium's natural barrier function is enhanced without requiring external structural modifications or de novo protein synthesis, allowing the system to self-regulate its permeability.

Inventive Principle:
Principle #25Self-service

2Ease of operation

If compounds modulating cytoskeletal tension are used to regulate tight junctions, then specific and reversible control of paracellular permeability is achieved, but complexity of the treatment mechanism increases

Engineering Contradiction:
Improvecontrol of tight junction opening and closingVSAvoidtreatment mechanism complexity
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The invention replaces complex structural modifications or de novo protein synthesis mechanisms with a simpler chemical approach. By using compounds that modulate cytoskeletal tension, the treatment achieves control of tight junction permeability through biochemical modulation rather than mechanical or genetic intervention, simplifying the overall treatment mechanism.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The treatment acts on the cytoskeletal tension before pathological changes occur or at the onset of disease. By modulating cytoskeletal tension in advance, the tight junctions are pre-conditioned to maintain appropriate permeability, preventing allergen and pathogen penetration before they can cause damage.

Inventive Principle:
Principle #10Preliminary action

3Stability of the object's composition

If preservatives like benzalkonium chloride are used in current treatments, then stability of the treatment solution is improved, but side effects and disruption of the ocular barrier occur

Engineering Contradiction:
Improvestability of treatment solutionVSAvoidside effects from preservatives
Core Design Contradiction:
Stability of the object's compositionVSObject-generated harmful factors

Solution Approach 1:

The invention extracts and removes the harmful preservative component (benzalkonium chloride) from the treatment formulation. By eliminating this preservative and relying instead on compounds that modulate cytoskeletal tension, the treatment maintains solution stability without causing side effects or disrupting the ocular barrier.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention converts the need for preservative stability into a benefit by using alternative compounds that modulate cytoskeletal tension. These compounds not only provide the necessary treatment effect but also inherently maintain solution stability without the harmful side effects associated with traditional preservatives, turning a potential harm into a beneficial property.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 provides a specific, fine, and reversible regulation of ocular surface epithelial permeability, reducing inflammation and preventing the penetration of allergens and pathogens, effectively managing ocular surface disorders and dry eye syndrome.

Implementation Method 1

The compositions and methods of the invention are based in particular on the use of agents or conditions modulating cytoskeletal tension of the epithelial cells of the conjunctiva and cornea

Methodology Applied
Scientific EffectCytoskeletal tension modulation:

Implementation Method 2

using inhibitors like ML-7 to inhibit myosin light chain kinase and other molecules that affect cytoskeletal contraction

Methodology Applied
Scientific EffectMyosin light chain kinase inhibition:

Implementation Method 3

absorption of large molecules and the passage of antigens and/or toxins occur principally by the paracellular route, at the level of 'tight junctions' located between epithelial cells

Methodology Applied
Scientific EffectParacellular transport: Permeation

Implementation Method 4

Epithelial tight junctions (TJ) are structures which link the cells lining mucosal epithelia. These flexible structures, attached to the cytoskeletal components composed of actin and myosin filaments

Methodology Applied
Scientific EffectTight junction structure:

Data Source

PatentUS8273708B2Methods of treatment of ocular surface pathologies
Publication Date: 2012.09.25 NEUROPTIS BIOTECH
  • US8273708B2 patent drawing
  • US8273708B2 patent drawing
  • US8273708B2 patent drawing

AI summary

The invention concerns compositions and methods for treating and/or preventing ocular pathologies. The invention also concerns compositions and methods enabling the regulation of paracellular permeability of the ocular epithelium. The compositions and methods of the invention are based in particular on the use of agents or conditions modulating the opening of tight junctions of the ocular epithelium. The invention can be used for preventive or curative treatment of various pathologies, such as pathologies of the ocular surface in mammals, particularly in human beings.