RESUMEN
INTRODUCTION: Dry eye disease (DED) is a multifactor-induced disease accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Traditional anti-inflammation agent corticosteroids applied in DED treatment could result in high intraocular pressure, especially in long-term treatment. Therefore, we explored a nano drug that aimed to block the formation pathway of DED which had anti-inflammatory, sustained release, and good biocompatibility characteristics in this study. METHODS: We prepared a novel nanomedicine (Tet-ATS@PLGA) by the thin film dispersion-hydration ultrasonic method and detected its nanostructure, particle size, and zeta potential. Flow cytometry was used to detect the cell survival rate of each group after 24 h of drug treatment on inflammed Statens Seruminstitut Rabbit Corneal (SIRC) cells. Observed and recorded corneal epithelial staining, tear film rupture time, and Schirmer test to detect tear secretion on the ocular surface of rabbits. The corneal epithelial thickness, morphology, and number of bulbar conjunctival goblet cells were recorded by H&E staining. Finally, we detected the expression of VEGF, IL-1ß, PGE2, and TNF-α by cellular immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). RESULTS: The encapsulation efficiency and drug loading of Tet-ATS@PLGA were 79.85% and 32.47%, respectively. At eye surface temperature, Tet can easily release from Tet-ATS@PLGA while that it was difficult to release at storage temperature and room temperature. After 2 weeks medication, Tet-ATS@PLGA can effectively improve the tear film rupture time and tear secretion time in a DED model (p <0.05). Compared with the normal group (62.34 ± 4.86 mm), the thickness of corneal epithelium in ATS (29.47 ± 3.21 mm), Tet-ATS (46.23 ± 2.87 mm), and Tet-ATS@PLGA (55.76 ± 3.95 mm) gradually increased. Furthermore, the flow cytometry indicated that Tet-ATS@PLGA can effectively promote the apoptosis of inflammatory SIRC cells, and the cellular immunofluorescence and ELISA experiments showed that the expression intensity of inflammatory factors such as VEGF, IL-1ß, PGE2, and TNF-α decreased in this process. Interestingly, Tet also had the effect of reducing intraocular pressure. CONCLUSION: Tet-ATS@PLGA can effectively promote the apoptosis of inflammatory corneal epithelial cells, thus inhibiting the expression of inflammatory factors to block the formation of DED and improve the secretion of tear on the ocular surface.
Asunto(s)
Síndromes de Ojo Seco , Nanopartículas , Animales , Conejos , Ácido Poliglicólico/análisis , Ácido Poliglicólico/metabolismo , Ácido Poliglicólico/uso terapéutico , Factor de Necrosis Tumoral alfa , Dinoprostona/análisis , Dinoprostona/metabolismo , Dinoprostona/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Síndromes de Ojo Seco/diagnóstico , Lágrimas/metabolismo , Córnea/metabolismo , Antiinflamatorios/uso terapéutico , Nanopartículas/químicaRESUMEN
Background: Purified platelet-rich plasma (P-PRP) is gradually being used in the treatment of osteoarthritis (OA), and its sources are mainly divided into autologous and allogeneic blood. However, it is unclear whether autologous PRP is more effective or allogeneic PRP is superior. Objective: In this study, autologous and allogeneic P-PRP was injected at early stage of KOA in rabbits, and then the differences in the efficacy of the two P-PRPs against KOA were compared from several perspectives, including pathological histology and immunohistochemistry. Method: Experimental rabbits were divided into normal group (n = 8), model group (n = 8), autologous P-PRP group (n = 8), and allogeneic P-PRP group (n = 8) using a random number table method. The normal and model groups did not receive any treatment, and the autologous P-PRP and allogeneic P-PRP groups received intra-articular injections of autologous and allogeneic P-PRP, respectively, to observe the changes in the gross specimens of the knee joints of the experimental rabbits in each group. The histopathological changes of chondrocytes were also observed by HE-stained sections of articular cartilage, and the expression of chondrocytes Bone morphogenetic protein-2 (BMP-2) and Sox9 were detected by immunohistochemistry. Results: Compared with the allogeneic P-PRP group, the differences were statistically significant (P < 0.05) in the gross specimens and pathological histological findings in the autologous PRP group. Immunohistochemical results showed that the expression of BMP-2 and Sox9 was elevated in both the autologous P-PRP group and the allogeneic P-PRP group compared with the model group, and the expression of BMP-2 was higher in the autologous P-PRP group than in the allogeneic P-PRP group, with a statistically significant difference (P < 0.05), while there was no difference in the expression of Sox9 between the two groups (P > 0.05). Conclusion: Intra-articular injection of autologous P-PRP activated the expression of BMP-2 and Sox9 in chondrocytes and effectively improved KOA cartilage repair and reduced bone redundancy and joint fluid formation, and its efficacy was superior to that of intra-articular injection of allogeneic P-PRP.