Insights & Discussion
Inflammation modulation—targeting innate immune signals and exploring epigenetic regulation, the gut microbiome, and herbal agents—emerges as a promising treatment strategy for retinitis pigmentosa.
The study's methodology began by identifying and emphasizing the role of neuroinflammation in the progression of retinitis pigmentosa (RP). It delved into the effects of continuous sterile inflammation, caused by abnormal activation of immunity, which leads to neuron loss and structural destruction in RP. The main focus of the research was to review therapeutic strategies, concentrating on the modulation of innate immune signals like Tumor Necrosis Factor alpha (TNFα) signaling, Toll-Like Receptor (TLR) signaling, NLRP3 inflammasome activation, chemokine signaling, and Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling.
Post this initial evaluation, the study proceeded to explore novel therapeutic strategies. It examined how the pattern of gene activation and deactivation (epigenetic regulation), the gut microbiome (the collection of microbes living in our intestines), and various herbal agents can serve as possible treatment paths for retinitis pigmentosa.
Discover Related Insights
The traditional Chinese medicine prescription combination of Chrysanthemi Flos, Cassiae Semen, Lycii Fructus, Angelicae Sinensis Radix and Salviae Miltiorrhizae Radix et Rhizoma presents potential for treating retinal diseases.
2024 Traditional Medicine Research Exploring a novel traditional Chinese medicine prescription containing Chrysanthemi Flos for retinal diseases: an integrated strategy of data mining and network pharmacology Zhang JX, Zhang KL, Chang XW, Gu JF, Wei SB, Zhu BY, et al.
Data Mining Chrysanthemum Retinitis Pigmentosa
Methodology: The researchers employed data mining to discern a new traditional Chinese medicine (TCM) prescription against retinal diseases and explore its medication rule. This was followed by constructing a network of TCMs, core ingredients, core targets, and core pathways using network pharmacology. The binding ability between core active ingredients and core targets was then verified through molecular docking and molecular dynamics simulation techniques.
Discussion: The novel TCM prescription screened in this study bears great potential in retinal diseases treatment through a unique mechanism of action. This mechanism involves TCM prescriptions that possess clearing heat and supplementing activities, associated with liver and lung meridians. The mechanism was found to act by modulating several core targets implicated in multiple core pathways such as the AGE-RAGE signaling pathway in diabetic complications, and the PI3K-Akt signaling pathway, among others. This potentially inhibits the inflammatory response, oxidative stress, and retinal neovascularization and apoptosis of retinal ganglion cells and retinal pigment epithelial cells. This improves retinal structural impairment and can have a significant impact on the treatment of retinal diseases.
Lycium barbarum polysaccharide may decrease apoptosis in retinal photoreceptor cells of retinitis pigmentosa mice by suppressing nuclear factor-kappa B/NOD-like receptor thermal protein domain-associated protein 3 pathway.
2023 Digital Chinese Medicine Inhibition of photoreceptor apoptosis in mice with retinitis pigmentosa through NF-κB/NLRP3 pathway suppression with Lycium barbarum polysaccharide Wang Y, Deng Y, Lu J, Peng J, Zhou Y, Yang Y, et al.
Experimental Study Retinitis Pigmentosa
The team carried out both in vivo and in vitro studies. Initially, mouse retinal ganglion cells were categorized into groups based on the doses of Lycium barbarum polysaccharide they were given and a positive drug control group. These cells were then subject to different H2O2 concentrations to induce apoptosis. Techniques such as flow cytometry, immunofluorescence, and western blot were used to evaluate cell viability, apoptosis rate, and expression of various markers. For in vivo research, the team used C57/BL6 and Rd10 mice divided into similar groups as the in vitro experiment. The mice underwent drug treatment for four weeks, after which their retina's response to light and general health were evaluated using an electroretinogram and histopathological examination.
The in vitro experiments showed that the apoptosis rate of ganglion cells significantly increased in the model group, along with up-regulation of certain proteins. However, a high dose of Lycium barbarum polysaccharide decreased the cell apoptosis rate and the levels of certain proteins. Similarly, in vivo testing showed that a high dose of the substance significantly aided in morphological alterations in a retina layer of Rd10 mice, and down-regulated the expression levels of a number of apoptosis-related proteins.
Zhangyanming Tablets show potential as a protective agent for retinal function in early-stage, genetically-caused blindness in mice, possibly due to their antioxidant and anti-/pro-apoptotic properties.
2023 Biomedicine & Pharmacotherapy Protective effect of ZYMT, a traditional Chinese patent medicine in a mouse model of retinitis pigmentosa Huang Z, Huang Q, Xu K, Liang L, Li Y, Zhou W, et al.
Experimental Study Dang Shen Ge Gen Goji Berry
Eighty mice with Retinitis Pigmentosa (RP) were divided into two groups, with one group receiving Zhangyanming Tablets (ZYMT) and a control group getting distilled water. After a period of 7 and 14 days, the researchers conducted tests through electroretinogram, fundus photography, and histological examination to assess the retinal function and structure of the subjects. They furthered the study using TUNEL, immunofluorescence and qPCR to evaluate cell apoptosis and the expressions of particular genes.
The ZYMT-treated mice displayed a notable enhancement in retinal reactions and overall preservation of retinal structure when compared to the control group. Particularly noticeable were increases in retinal thickness and cell count, alongside a significantly lowered rate of cell death. A comprehensive follow-up shows the altered expressions of several genes in the retina following the application of ZYMT. These results, combined, suggest a key role of ZYMT in mitigating the effects of RP especially in early stages.
The Chinese herbal medicine Bujing Yishi tablets could alleviate photoreceptor degeneration in retinitis pigmentosa by inhibiting microglial over-activation and inflammation.
2023 Phytomedicine Bujing Yishi tablets alleviate photoreceptor cells death via the P2X7R/CX3CL1/CX3CR1 pathway in Retinitis Pigmentosa rats Qi Y, Liu L, Liang D, Tang S, Yu X, Ye H, et al.
Experimental Study Bu Jing Yi Shi Tablets Retinitis Pigmentosa
This experiment began with the creation of a rat model for retinitis pigmentosa through intraperitoneal injection of N-Methyl-N-Nitrosourea. After the rats developed retinal degeneration, they were treated with Bujing Yishi tablets. To confirm the impact of these tablets on the rat model, the researchers conducted several tests, including examination of the retinal cytokine levels and expression of IBA-1 in microglia. This let them monitor the apoptotic cells, ONL thickness, retinal morphology, and photoreceptor degeneration. They further used western blot, real-time polymerase chain reaction, and immunofluorescence to determine the mRNA and protein expression levels involved in the P2X7R/CX3CL1/CX3CR1 pathway.
Following the treatment of the rats with Bujing Yishi tablets, there was significant relief in the morphological structure deterioration of the retinas and the photoreceptor degeneration. The herbal tablets also reduced the number of apoptotic cells in the ONL and prevented the thinning of the ONL, pointing to their effectiveness in retinal preservation. Additionally, the tablets lowered the level of over-activated microglia and decreased retinal levels of inflammatory markers. Bujing Yishi tablets were also observed to decrease the protein and mRNA expression of P2X7, CX3CL1, and CX3CR1, further exhibiting their mechanism of retinal preservation through influence on the P2X7R/CX3CL1/CX3CR1 pathway.
Fructus Lycii and Salvia miltiorrhiza Bunge extract (FSE) shows potential as a clinical treatment for retinitis pigmentosa by inhibiting photoreceptor cell death following oxidative stress.
2023 Biomedicine & Pharmacotherapy Fructus Lycii and Salvia miltiorrhiza Bunge extract attenuate oxidative stress-induced photoreceptor ferroptosis in retinitis pigmentosa Yang Y, Wang Y, Deng Y, Lu J, Xiao L, Li J, et al.
Experimental Study Dan Shen Retinitis Pigmentosa
The study utilized hydrogen peroxide to induce oxidative stress in 661 W cells, which were examined with flow cytometry and an enzyme-linked immunosorbent assay. The impact of this oxidative stress on the cells’ mitochondria was observed using an electron microscope to understand the nature of cell death. The study also analyzed the compensatory effect of the Fructus Lycii and Salvia miltiorrhiza Bunge extract on the retinal structure and function of rd10 mice using histopathological examination, fundus photographs, and electroretinography. Protein levels were evaluated using Western blot assays, specifically targeting proteins including Tumor Protein p53, Solute Carrier Family 7 Member 11, Glutathione peroxidase 4, Arachidonate-12-Lipoxygenase, and Dipeptidyl peptidase 4.
The results showed that hydrogen peroxide-induced oxidative stress in 661 W cells increased oxidative stress products and certain protein expressions, while decreasing others. Notably, the activation of Glutathione peroxidase 4 did not lessen reactive oxygen species generation and had little impact on cell death. The research discovered that both Ferrostatin-1 and the extract could lessen reactive oxygen species generation and inhibit cell death of photoreceptors in retinitis pigmentosa, achieving this by inhibiting the expression of one protein and increasing the expression of two others.
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