ABSTRACT
Treating posterior segment and retinal diseases poses challenges due to the complex structures in the eye that act as robust barriers, limiting medication delivery and bioavailability. This necessitates frequent dosing, typically via eye drops or intravitreal injections, to manage diseases, often leading to side effects with long-term use. Suprachoroidal injection is a novel approach for targeted drug delivery to the posterior segment. The suprachoroidal space is the region between the sclera and the choroid and provides a potential route for minimally invasive medication delivery. Through a more targeted delivery to the posterior segment, this method offers advantages over other routes of administration, such as higher drug concentrations, increased bioavailability, and prolonged duration of action. Additionally, this approach minimizes the risk of corticosteroid-related adverse events such as cataracts and intraocular pressure elevation via compartmentalization. This review focuses on preclinical and clinical studies published between 2019 and 2023, highlighting the potential of suprachoroidal injection in treating a variety of posterior segment diseases. However, to fully harness its potential, more research is needed to address current challenges and limitations, such as the need for technological advancements, refinement of injection techniques, and consideration of cost and accessibility factors. Future studies exploring its use in conjunction with biotech products, gene therapies, and cell-based therapies can lead to personalized treatments that can revolutionize the field of ophthalmology.
ABSTRACT
In the present study, we examine the neuroprotective role of the external Qi of YXLST in cultured retinal neurons. Primary retinal neuronal cultures were grown from retinas of 0-2-day-old Sprague-Dawley rats. Cultures were treated directly with external Qi of YXLST 30 min prior to H(2)O(2) exposure in most experiments. Cell viability was measured by 3,(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay. Apoptotic cell death was evaluated by the TdT-mediated digoxigenin-dUTP nick-end labeling TUNEL assay, and by DNA laddering analysis. Northern blot analysis was performed to examine the level of insulin-like growth factor-I (IGF-I) gene expression. Phosphatidylinositol 3-kinase (PI3K) assay was performed to study the PI3K activity. The results showed that treatment of external Qi of YXLST significantly attenuated neuronal death that was induced by 24-h exposure to hydrogen peroxide, and greatly inhibited hydrogen peroxide-induced apoptosis. External Qi of YXLST also upregulated IGF-I gene expression and increased PI3K activity. These observations indicate that external Qi-mediated IGF-I expression and PI3K signaling could be one of the mechanisms in neuroprotection by YXLST.
Subject(s)
Insulin-Like Growth Factor I/metabolism , Neurons/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Qi , Retina/cytology , Animals , Animals, Newborn , Blotting, Northern/methods , Cell Count/methods , Cell Death/drug effects , Cell Survival , Cells, Cultured , Female , Hydrogen Peroxide/toxicity , In Situ Nick-End Labeling/methods , Male , Neurons/drug effects , Neuroprotective Agents , Pregnancy , RNA/metabolism , Rats , Retina/drug effects , Time FactorsABSTRACT
We have previously reported that XY99-5038, a preparation from a specific formula of Traditional Chinese Medicine, could effectively inhibit hydrogen peroxide-induced retinal cell death. In the present study, we investigated the possibility of XY99-5038 to prolong neuronal survival in a long-term retinal neuronal culture. Basic fibroblast survival factor (bFGF), a potent neurotrophic factor, was employed as comparable agent. Retinas of 0-2 days old Sprague-Dawley rats were isolated and dissociated. The cells were maintained in tissue culture for up to 9 weeks in a synthetic serum-free media. XY99-5038 (100 ng/ml) or a vehicle was added to culture every 3-4 days, starting at the first week of culturing. The number of cells were counted and compared for each time point and treatment. Cell viability was also determined by MTT assay, whereas apoptotic cell death was evaluated by the TUNEL assay. XY99-5038 treatment significantly reduced cell loss, increased cell viability, and inhibited apoptosis in this long-term retinal neuronal culture. Our data also show that the protective effect of XY99-5038 is more potent than that of bFGF. Our data suggest that XY99-5038 could be beneficial to the prolongation of neuron survival.
