Cross-linked Hydrogel for Chronic Intraocular Pressure Elevation
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Solution Overview
Problem
Current animal models for glaucoma research fail to replicate chronic and moderate elevation of intraocular pressure (IOP), often resulting in transient IOP spikes, cataract development, and obscured optical media, limiting their effectiveness in studying retinal ganglion cell degeneration and neuroprotective therapies.
Innovation Solution
A method involving the injection of a crosslinkable polymer solution into the eye to form a cross-linked hydrogel, which obstructs aqueous humor drainage, leading to sustained IOP elevation for days to months, using temperature or pH-responsive polymers like hyaluronic acid or polyethylene glycol, allowing for controlled gelation and preventing optical media opacity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If conventional methods (hyper tonic saline, microbeads, hyaluronic acid) are used to elevate intraocular pressure, then IOP elevation is achieved, but the elevation is transient with high IOP spikes and does not recapitulate chronic moderate elevation observed in glaucoma patients
Solution Approach 1:
The invention changes the physical state parameter of the hydrogel from liquid (injectable) to solid (gel) in situ within the eye. This parameter change allows the material to remain in place for chronic elevation without causing transient spikes, reliably replicating glaucoma conditions over months
Solution Approach 2:
The invention uses composite hydrogel materials formed by crosslinking polymer chains. These composite structures provide sustained IOP elevation by combining the properties of water-absorbing polymers with crosslinking agents, creating a stable gel that maintains moderate pressure elevation chronically without the transient spikes seen in conventional methods
2Productivity
If high IOP elevation is induced to study glaucoma mechanisms, then retinal ganglion cell degeneration is accelerated, but retinal ischemia occurs as a harmful side effect
Solution Approach 1:
The invention changes the IOP elevation parameter from high/acute to moderate/chronic. By controlling the hydrogel formulation and crosslinking density, the system maintains IOP at moderately elevated levels that promote ganglion cell degeneration over time without reaching the high pressure thresholds that cause retinal ischemia
Solution Approach 2:
The invention creates a dynamic equilibrium where the hydrogel gradually absorbs water and expands to reach a stable volume. This dynamic process allows IOP to stabilize at moderate levels rather than spiking to high levels, enabling chronic degeneration studies without ischemic damage
3Duration of action of stationary object
If current glaucoma models are used, then IOP elevation is achieved, but cataract and corneal opacities develop obscuring in vivo examination
Solution Approach 1:
The invention applies local quality by placing the hydrogel specifically in the anterior chamber or vitreous humor where it can elevate IOP without affecting the optical media. The hydrogel's localized presence allows chronic IOP elevation while maintaining clear cornea and lens for prolonged in vivo imaging
Solution Approach 2:
The hydrogel's porous structure allows it to absorb and retain water while maintaining transparency. This porous network enables the gel to exert sustained osmotic pressure for chronic IOP elevation without becoming opaque, allowing clear optical media for months
4Stress or pressure
If transient IOP spikes are produced in animal models, then some IOP elevation is achieved, but the model does not recapitulate chronic moderate elevation observed in glaucoma patients
Solution Approach 1:
The invention utilizes phase transition from liquid to gel state. The injectable hydrogel is administered as a liquid that can be easily injected, then transitions to a gel state in situ, providing sustained IOP elevation. This phase change enables the system to maintain stable pressure elevation for months rather than transient spikes
Solution Approach 2:
The hydrogel provides continuous IOP elevation through its water-absorbing and expanding properties. As the gel gradually absorbs aqueous humor and expands, it maintains sustained pressure on the outflow tract, creating continuous moderate elevation that replicates chronic glaucoma conditions without interruption or transient spikes
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 creates a reliable animal model with chronic, moderate IOP elevation, enabling prolonged retinal ganglion cell degeneration studies while maintaining clear optical media for in vivo monitoring, facilitating the identification of compounds modulating IOP and retinal ganglion cell survival.
Implementation Method 1
permitting crosslinking of the polymer to form a cross-linked hydrogel in the eye
Implementation Method 2
form a cross-linked hydrogel in the eye
Implementation Method 3
which obstructs aqueous humor drainage, leading to sustained IOP elevation
Implementation Method 4
the polymer is a temperature responsive polymer or a pH responsive polymer
Implementation Method 5
the polymer is a temperature responsive polymer or a pH responsive polymer
Data Source
AI summary
The present invention provides a method for inducing chronic elevation of intraocular pressure in the eyes of an animal by introducing into the eyes a cross-linking hydrogel, an animal produced by this method, as well as a screening method useful for identifying compounds capable of modulating intraocular pressure as well as for identifying compounds capable of modulating retinal ganglion cell survival and/or regeneration.