Targeted degradation of VEGF with bispecific aptamer-based LYTACs ameliorates pathological retinal angiogenesis.

Rationale: Neovascular ocular diseases (NODs) represent the leading cause of visual impairment globally. Despite significant advances in anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF), persistent challenges remain prevalent. As a proof-of-concept study, we herein demonstrate the effectiveness of targeted degradation of VEGF with bispecific aptamer-based lysosome-targeting chimeras (referred to as VED-LYTACs). Methods: VED-LYTACs were constructed with three distinct modules: a mannose-6-phosphate receptor (M6PR)-binding motif containing an M6PR aptamer, a VEGF-binding module with an aptamer targeting VEGF, and a linker essential for bridging and stabilizing the two-aptamer structure. The degradation efficiency of VED-LYTACs via the autophagy-lysosome system was examined using an enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. Subsequently, the anti-angiogenic effects of VED-LYTACs were evaluated using in vitro wound healing assay, tube formation assay, three-dimensional sprouting assay, and ex vivo aortic ring sprouting assay. Finally, the potential therapeutic effects of VED-LYTACs on pathological retinal neovascularization and vascular leakage were tested by employing mouse models of NODs. Results: The engineered VED-LYTACs promote the interaction between M6PR and VEGF, consequently facilitating the translocation and degradation of VEGF through the lysosome. Our data show that treatment with VED-LYTACs significantly suppresses VEGF-induced angiogenic activities both in vitro and ex vivo. In addition, intravitreal injection of VED-LYTACs remarkably ameliorates abnormal vascular proliferation and leakage in mouse models of NODs. Conclusion: Our findings present a novel strategy for targeting VEGF degradation with an aptamer-based LYTAC system, effectively ameliorating pathological retinal angiogenesis. These results suggest that VED-LYTACs have potential as therapeutic agents for managing NODs.

[Observation of the efficacy of endoscopic myringoplasty with homoplastic amniotic membrane].

OBJECTIVE: To explore the clinical effectiveness of endoscopic myringoplasty with homoplastic amniotic membrane. METHOD: A retrospective study in 43 patients underwent endoscopic myringoplasty with homoplastic amniotic membrane was observed at the wound healing of tympanic membrane perforation and the hearing improve-threshold audiometry in 43 patients after surgery. RESULT: The tympanic membrane's perforation healing rate was 95.3% (41/43), and air conduction threshold audiometry in language frequency improved average 10 dB. The follow up was 1--4 years, and no recurrence or complications had occurred. CONCLUSION: The endoscopic myringoplasty could be able to simple myringoplasty whose air conduction threshold audiometry in language frequency was less than 40 dB. It could be used to repair not only the central perforation in tympanic membrane, but also the marginal perforation which has residual tympanic membrane in most of the regional. Human amniotic membrane is an ideal materials for repair of tympanic membrane.

[Clinical study of 26 patients with osteoma in the external].

OBJECTIVE: To summarize the experience of diagnosis and treatment on osteoma in the external auditory canal. METHOD: Retrospective study were undertaken in 26 patients with osteoma in the external auditory canal operated in author's unit. RESULT: Osteomas were removed through interauricular approach in all patients and confirmed by histopathological examination. The hearing of 22 patients with conductive hearing loss became normal after operation. The air conduction hearing threshold in 2 patients with mixed hearing loss improved average 15 dB and 20 dB respectively after operation. The follow up was more than 1 year, and no recurrence or complications had occurred. CONCLUSION: Osteoma in the external auditory canal is an uncommon benign lesion. The method of choice in diagnosis is temporal bone CT scan. Osteoma must be distinguished from exostosis in the external auditory canal. Osteoma is confirmed by pathological diagnosis and surgery is the only method for treatment.