Osteoarthritis (OA) is a common joint disorder characterized primarily by cartilage degeneration and osteophyte formation, leading to a substantial decline in patients' quality of life. Temporomandibular joint OA (TMJOA) is a degenerative lesion within temporomandibular joint disorders, accounting for approximately 8%-16% of diagnosed cases. Its clinical manifestations include joint pain, limited mouth opening, joint noises, and related symptoms. Cellular senescence plays a pivotal role in OA pathogenesis. Senescent processes contribute to functional impairment of chondrocytes, synovial cells, and osteocytes through multiple signaling pathways. DNA damage, telomere attrition, oxidative stress, and the release of inflammatory mediators are major drivers of cellular senescence. However, current literature lacks a systematic integration of senescence-related mechanisms in OA and TMJOA. Furthermore, anti-aging therapeutic strategies for these conditions lack targeted approaches that account for interactions among distinct senescence mechanisms. This review elucidates the various characteristic types of cellular senescence, their interactions, and the senescence-induced pathogenesis of OA and TMJOA. A comprehensive investigation into the mechanisms of cellular senescence may yield novel insights and inform the development of therapeutic strategies for managing OA.
Purpose: This study aimed to develop artificial intelligence models for predicting postoperative functional outcomes in patients with rhegmatogenous retinal detachment (RRD). Methods: A retrospective review and data extraction were conducted on 184 patients diagnosed with RRD who underwent pars plana vitrectomy (PPV) and gas tamponade. The primary outcome was the best -corrected visual acuity (BCVA) at three months after the surgery. Those with a BCVA of less than 6/18 Snellen acuity were classified into a vision impairment group. A deep learning model was developed using presurgical predictors, including ultra-widefield fundus images, structural optical coherence tomography (OCT) images of the macular region, age, gender, and preoperative BCVA. A fusion method was used to capture the interaction between different modalities during model construction. Results: Among the participants, 74 (40%) still had vision impairment after the treatment. There were significant differences in age, gender, presurgical BCVA, intraocular pressure, macular detachment, and extension of retinal detachment between the vision impairment and vision non -impairment groups. The multimodal fusion model achieved a mean area under the curve (AUC) of 0.91, with a mean accuracy of 0.86, sensitivity of 0.94, and specificity of 0.80. Heatmaps revealed that the macular involvement was the most active area, as observed in both the OCT and ultra-widefield images. Conclusions: This pilot study demonstrates that artificial intelligence techniques can achieve a high AUC for predicting functional outcomes after RRD surgery, even with a small sample size. Machine learning methods identified The macular region as the most active region. Translational Relevance: Multimodal fusion models have the potential to assist clinicians in predicting postoperative visual outcomes prior to undergoing PPV.
OBJECTIVE:To evaluate the effect of 0.2% ambroxol eye drop on tear secretion and corneal healing on a rabbit dry eye model, and to delineate potential underlying mechanisms.MATERIALS AND METHOD:A mixed mechanism dry eye model was created using 12 healthy New Zealand rabbits by excision of the main lacrimal glands, Harderian gland and nictitating membrane. Establishment of the model was confirmed by the decrease of Schirmer I and increase of corneal fluorescein staining scores. Two weeks after model creation, the rabbits were randomly and evenly divided into NaCl, 0.1% sodium hyaluronate and 0.2% ambroxol groups. Each group was administered the respective eye drops 4 times a day for four weeks. The Schirmer I test and corneal fluorescein staining were performed at two and four weeks. After four weeks of treatment, the animals were sacrificed and the conjunctiva and eyelid specimens collected. Inflammatory factors IL-8, TNF-α, and goblet cell specific mucin MUC5AC were measured by ELISA while the lid meibomian gland was evaluated by oil red O staining.RESULTS:Compared with the baseline, 2 weeks after the surgery, Schirmer I test value decreased significantly (20.35 ± 5.18 mm/5 min vs 13.95 ± 4.64 mm/5 min, p < 0.01), and the fluorescein staining score increased significantly (0.5 ± 0.6 vs 5.5 ± 1.4, p < 0.01). After four weeks of treatment, compared with the NaCl and sodium hyaluronate groups, tear secretion in ambroxol group increased significantly (p < 0.01), while the corneal fluorescence staining score decreased significantly (p < 0.01). In the conjunctival tissue, significant decrease was seen in TNF-α (p < 0.01) and IL-8 [p (unilateral) < 0.05] concentrations in ambroxol group, and significant increase in MUC5AC concentration (p < 0.01) in ambroxol group as well. The lipid content in the lid meibomian glands appeared increased after the administration of ambroxol.CONCLUSION:The present rabbit dry eye model study demonstrated potentials of topically administered 0.2% ambroxol in stimulating tear and mucin secretion, inhibiting ocular surface inflammation, promoting corneal healing, and possibly augmenting meibomian gland lipid production.
Bromhexine was reported to relieve the symptoms of Sjogren Syndrome at an early stage. However, the underlying mechanism remains unclear. Here, we administered bromhexine at low doses in human primary conjunctival fornix epithelial cells, and found it stimulated MUC5AC secretion and lipid droplet production. Expression of the metabolism-related gene CHML was also upregulated by bromhexine treatment, and REP2, the protein produced by the CHML gene, was induced. These results suggest that bromhexine is a potential candidate eye drop drug for the treatment of multiple types of dry eye disease, not only limited to the treatment of dry eyes in Sjogren Syndrome.
The relationship between aquaporin (AQP) 5 and mucin (MUC) 5AC in the conjunctiva was investigated in response to acute dry eye (DE) stress. A mixed-mechanism rabbit DE model, in which the main lacrimal gland, Harderian gland, and nictitating membrane were resected, was further explored in this study. Conjunctival impression cytology specimens were harvested before excision (BE) and up to 3 months after excision (AE) in 8 (16 eyes) male New Zealand White rabbits, and immunoblotting was employed to assess the expression of AQP5 and MUC5AC. It was observed that AQP5 and MUC5AC showed a positive, synchronous expression pattern with progressive upregulation at protein level up to 2 months AE. At 3 months, the expression of both proteins decreased, but was still higher than that of BE. Such a synchronous relationship was further observed in mouse conjunctiva epithelium primary cells under hyperosmotic condition. Moreover, the co-immunoprecipitation of AQP5 and MUC5AC suggested a possible physical interaction between the two molecules. Our data indicates that conjunctival AQP5 and MUC5AC act synchronously in response to acute DE stress.