This story is part of a series on the current progression in Regenerative Medicine. This piece is part of a series dedicated to the eye and improvements in restoring vision. 


In 1999, I defined regenerative medicine as the collection of interventions that restore tissues and organs damaged by disease, injured by trauma, or worn by time to normal function. I include a full spectrum of chemical, gene, and protein-based medicines, cell-based therapies, and biomechanical interventions that achieve that goal.


Retinitis pigmentosa is a debilitating disease that causes the death of photoreceptor cells and leads to vision loss. While regulating intraretinal inflammation effectively slows the disease’s progression, a reliable anti-inflammatory treatment strategy is still lacking. Recently, researchers have developed a hyaluronic acid-based inflammation-responsive hydrogel that could potentially delay vision loss in retinitis pigmentosa patients. 


The study published in npj Regenerative Medicine details the creation of the hydrogel and its effects on retinal degeneration through epigenetic regulation. The injectable hydrogel responds to cathepsin overexpression in an inflammatory environment. An epigenetic drug, the enhancer of zeste homolog 2 (EZH2) inhibitor, is incorporated into the hydrogel to reduce inflammatory factors. The hydrogel demonstrates on-demand anti-inflammatory effects on microglia cells in both in vitro and in vivo retinal degeneration models.


What is a Hydrogel?


Hydrogels are a unique gel-type comprising a three-dimensional network of hydrophilic polymer chains. These chains can absorb much water within their structure, making them ideal for various applications. By regulating the composition and crosslinking of the polymer chains, we can modify the properties of hydrogels to match specific requirements.


The versatility of hydrogels enables their use in a wide range of applications in various fields. They are regularly employed in the medical industry for wound dressings, drug delivery systems, and tissue engineering. In agriculture, hydrogels enhance soil water retention and plant growth. In the cosmetics industry, they are used in skincare products to provide hydration and moisturization to the skin.


Hydrogels have the advantage of being customizable to specific needs. The stiffness and elasticity of the hydrogel can be adjusted by varying the crosslinking density of the polymer chains. Furthermore, the hydrogel’s swelling capacity in response to changes in temperature, pH, or the presence of certain chemicals can also be fine-tuned.


A Hydrogel for Retinitis Pigmentosa


In the case of the hydrogel being discussed, it is precisely engineered using DBCO-conjugated hyaluronic acid crosslinked with a cathepsin-cleavable crosslinker. This means that the hydrogel is designed to allow it to react to the presence of cathepsin, an enzyme found in the inflammatory microenvironment. When cathepsin is detected, the hydrogel breaks down and releases the encapsulated EZH2 inhibitor, which helps regulate inflammation. 

The hydrogel, containing the drug, is injected into the eyeball. Once injected, the hydrogel would disassemble due to over-secreted cathepsins in the inflammatory retinal microenvironment, releasing the pre-loaded EZH2 inhibitor. The hydrogel effectively reduced inflammation by delivering the EZH2 inhibitor on demand in response to inflammatory activities from the early stage of RP.


Doctors will be able to administer treatment more precisely and effectively with a new approach. This will help to reduce inflammation and slow down the progression of retinitis pigmentosa, a significant breakthrough in the fight against this disease. The innovation in drug delivery allows for a targeted approach, delivering treatment when and where it is needed.


What The Preclinical Study Found


The study shows that the new hydrogel formula effectively reduces inflammation within the retina and protects photoreceptors’ structural and functional integrity. This hydrogel also slows down the progression of retinitis pigmentosa, delaying vision loss. In addition, the hydrogel’s anti-inflammatory properties specifically target microglia cells and have been thoroughly tested in both in vitro and in vivo models of retinal degeneration.


This hydrogel is in the preclinical phase, and preclinical studies have shown its potential. The hydrogel effectively reduces inflammation by delivering the EZH2 inhibitor on demand in response to early-stage retinitis pigmentosa inflammation. It protects photoreceptors structurally and functionally.


Developing a hydrogel based on hyaluronic acid that responds to inflammation is a promising approach for treating retinitis pigmentosa. The on-demand drug delivery system can reduce side effects and optimize therapeutic effects by adjusting the drug amount based on the severity of the disease. Although clinical trials are still needed, the hydrogel shows excellent potential in preclinical studies, offering hope for patients with retinitis pigmentosa.

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