Retinal ganglion cells (RGCs), the projection neurons of the eye, are irreversibly lost once the optic nerve is injured, which is a critical mechanism of glaucoma. Mobile zinc (Zn2+) levels rapidly increase in retinal interneuron amacrine cells and Zn2+ is then transferred to RGCs via the Zn2+ transporter protein ZnT-3, triggering RGC loss in optic nerve injury. Zn2+ chelation and ZnT-3 deletion promote long-term RGC survival. However, the downstream signaling pathways of Zn2+ in RGCs remains unknown. Here, we show that increased levels of Zn2+ upregulate the expression and activity of mitochondrial zinc metallopeptidase OMA1 in the retina, leading to the cleavage of DELE1 and activation of cytosolic eIF2α kinase PKR, triggering the integrated stress response (ISR) in RGCs. Our study identified OMA1 and ISR as the downstream molecular mechanisms of retinal Zn2+ and potential targets for preventing the progression of Zn2+-associated neuronal damage.
Neurodegenerative disorders are characterized by typical neuronal degeneration and axonal loss in the central nervous system (CNS). Demyelination occurs when myelin or oligodendrocytes experience damage. Pathological changes in demyelination contribute to neurodegenerative diseases and worsen clinical symptoms during disease progression. Glaucoma is a neurodegenerative disease characterized by progressive degeneration of retinal ganglion cells (RGCs) and the optic nerve. Since it is not yet well understood, we hypothesized that demyelination could play a significant role in glaucoma. Therefore, this study started with the morphological and functional manifestations of demyelination in the CNS. Then, we discussed the main mechanisms of demyelination in terms of oxidative stress, mitochondrial damage, and immuno-inflammatory responses. Finally, we summarized the existing research on the relationship between optic nerve demyelination and glaucoma, aiming to inspire effective treatment plans for glaucoma in the future.
A reliable animal model providing chronic and persistent ocular hypertension and characteristic neurodegeneration is essential to recapitulate human glaucoma and understand the underlying pathophysiological mechanisms behind this disease. Many approaches...
Objective: To explore the application of new media assisted Team-Based Learning (TBL) teaching model on the pre-internship curriculum of ophthalmology for medical students, thus providing a reference for the teaching reform of the pre-internship curriculum. Methods: In July 2022, 60 medical students from grades 2019 and 2020 were selected as the research subjects and were randomly divided into two groups. 30 students joined the new media assisted TBL teaching model group and 30 students joined the conventional TBL teaching model group. The effect of the new media assisted TBL teaching model and TBL teaching models was evaluated by TBL homework scores, ophthalmology-related examination scores, curriculum evaluation, self-evaluation after class, and the questionnaire about employment choice. Statistical analysis was performed using a nonparametric test and Chi-square analysis. Results: Among seven classroom assignments, one of them was scored statistically higher in the new media group than the traditional group (Z=-2.252, P=0.048). In ophthalmology-related examination scores, there was no significant difference between the new media group and the traditional group (Z=-0.277, P=0.788), while the excellent rates in the new media group (86.67%) were significantly higher than that in the traditional group (63.33%) (χ 2 =4.356, P=0.037). In the curriculum evaluation, all students were very satisfied with the pre-internship curriculum, more than 90% of them approved of the teaching methods such as mini-lessons and TBL, and 88.3% of the students (53/60) thought that the new media group is better than traditional TBL, and 58.3% of them (35/60) are very satisfied with new media. There was no statistically significant difference in self-evaluation between the new media group and the traditional group. In terms of employment choice, the new media group has more diversified choices. Conclusions: Both teaching modes produced fine learning outcomes in the pre-internship curriculum of ophthalmology for junior medical students. The new media assisted teaching model seemed to benefit the outcomes of the TBL classroom in terms of promoting learning enthusiasm and hands-on capability, consolidating the mastery of theoretical knowledge, and inspiring medical students to think about career planning in a more diversified way.
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