Effective protection of photoreceptors using an inflammation-responsive hydrogel to attenuate external retinal degeneration Summary Retinitis pigmentosa (RP) is a degenerative disease of the outer retina that can lead to the death of photoreceptor cells and profound vision loss. Although effective regulation of intraretinal inflammation can slow down disease progression, an effective anti-inflammatory treatment strategy is still lacking. This study reports the fabrication of a hyaluronic acid- based inflammation-responsive hydrogel (IRH) and its epigenetic regulatory effects on retinal degeneration. Injectable IRH was designed to respond to cathepsin overexpression in an inflammatory environment. The epigenetic drug, zeste homolog 2 (EZH2) inhibitor enhancer, was loaded into the hydrogel to attenuate inflammatory factors. The on-demand anti-inflammatory effects of microglia cells via drug-loaded IRH were verified in retinal degeneration 10 (rd10) mouse models in vitro and in vivo . Therefore, our IRH not only reduced intraretinal inflammation but also protected photoreceptors morphologically and functionally. Our results suggest that the IRH reported here can be used to considerably delay vision loss caused by retinitis pigmentosa (RP). |
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Interactive release of anti-inflammatory drugs depending on the level of retinal degeneration. It is hoped that a personalized treatment approach will be developed to reduce patients’ discomfort when receiving multiple injections.
The Korea Institute of Science and Technology (KIST) announced that Dr. Maesoon Im of the Brain Science Institute, together with Prof. Seung Ja Oh of Kyung Hee University and Prof. Kangwon Lee of Seoul National University, joined with anti-inflammatory medications successfully in a hydrogel to suppress inflammation in the retina and effectively deliver the medications to the inflamed area.
Age-related macular degeneration and retinitis pigmentosa are incurable eye diseases that cause blindness due to gradual damage to photoreceptor cells, which convert light into biological signals in the retina, the light-sensitive tissue at the back of the eye. . Age-related macular degeneration is a condition that damages the macula, the central part of the retina, and is the leading cause of blindness in people over 65 years of age. Retinitis pigmentosa, on the other hand, is a genetic disorder that causes gradual death of photoreceptor cells in the retina and affects approximately 1 in 4,000 people worldwide; It initially causes night blindness but eventually leads to vision loss.
Currently, there is no effective cure for either disease and one treatment involves injecting anti-inflammatory drugs into the eye to slow the degree of damage to the retina. However, these injections only work as long as the drug remains in the eye, requiring patients to visit a clinic for intraocular injections every four to 12 weeks, depending on how long the drug’s effect lasts.
For the first time, the team used a substance that inhibits the inflammatory factor EZH2, which contributes to retinal degeneration, together with an anti-inflammatory agent. When mice with retinal degeneration were injected with the anti-inflammatory drug, the progression of retinal degeneration slowed.
Researchers have successfully developed a hydrogel that slowly degrades upon encountering the enzyme cathepsin, which is normally overexpressed in inflammatory environments, to deliver anti-inflammatory drugs. When the team’s drug-loaded, inflammation-sensitive hydrogel was injected into the eyes of mice suffering from retinal degeneration, inflammatory factors in the retina were reduced to about 6.1%.
The team also found that the protective effect on photoreceptor cells , which are known to be destroyed by retinal degeneration, was approximately four times greater than in the control group, effectively delaying vision loss.
In particular, hyaluronic acid- based hydrogel , which has mechanical and optical properties similar to those of the eye’s vitreous humor, allows for different rates of hydrogel degradation in each patient, minimizing the need for repeated injections. This newly developed technology is expected to reduce the financial burden and risk of accidents during outpatient visits for patients with mobility difficulties due to visual impairment. Additionally, for patients in the early stages of symptoms, reducing the frequency of hospital visits can alleviate discomfort in daily life.
"For future commercialization, we plan to digitize the amount of drug and hydrogel used, as well as the treatment period, according to the progression of the disease. We also intend to evaluate the long-term stability of the drug delivery system," said Dr. Maesoon I’m from KIST. "In addition to retinal degenerative diseases, we will investigate inflammation levels in other retinal diseases to see if our inflammation-responsive drug delivery system would work in those conditions," said Professor Seung Ja Oh of the University Kyung Hee.
