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Eysteinsson, T.

Publications and source records attributed to Eysteinsson, T..

3 recordsLinked to original sources

MITF is essential for autophagy in the retinal pigment epithelium

The Microphthalmia-associated transcription factor (MITF) plays a critical role in retinal pigment epithelium (RPE) development and function. Dysfunctional autophagy and lysosomal degradation in the RPE have been implicated in age-related retinal degeneration, yet the contribution of MITF to these pathways remains incompletely understood. Here, we show that reduced Mitf expression impairs autophagy in mouse and human RPE cells. Primary RPE cells from Mitfmi-vga9/+ heterozygotes mice displayed altered autophagic flux characterized by accumulation of LC3B-II and p62, while MITF knockdown in human ARPE-19 cells promoted autophagosome accumulation. Ultrastructural analysis further revealed age-dependent accumulation of autolysosomes and lipofuscin-like granules in mutant RPE cells. In addition, expression of autophagy-related genes was altered in mutant RPE tissue, supporting disrupted lysosomal-autophagic homeostasis. Together, our findings identify MITF as an important regulator of autophagy in the RPE and suggest that impaired MITF-dependent homeostasis may contribute to retinal degeneration.

cell biology↗

Enhancing Medical Science Engagement through International Research Exchange: Objectives, Activities, and Outcomes

BackgroundThe global decline in the number of physician-scientists, despite an increase in practicing physicians, underscores a critical need for integrating research training into medical education. Addressing this issue, we established an international research exchange program aimed to enhance scientific literacy, foster transferable skills, and align curricula with European standards through collaborative research experiences. MethodologyThe program enabled reciprocal student mobility, involving eleven medical undergraduates who conducted month-long basic science research projects. Participants also completed comprehensive pre-training in scientific communication, safety protocols, and ethics, and were required to participate in local public engagement events. Feedback from participants, which we present here, was collected via three anonymous, voluntary questionnaires: pre-program, post-program and post-1-year follow-up, which we provide here to support similar initiatives. ResultsDespite challenges and delays due to the COVID-19 pandemic, the program met its objectives, demonstrating adaptability and effective resource management. Feedback revealed significant improvements in participants confidence in research methodologies, critical appraisal of scientific literature, and motivation for future research involvement. ConclusionThis project highlights the potential of structured international exchange programs, particularly among smaller institutions, to address gaps in medical education, enhance scientific training and opportunities in translational research for undergraduates, and cultivate the next generation of physician-scientists.

scientific communication and education↗

Mitf links neuronal activity and long-term homeostatic intrinsic plasticity

Neuroplasticity forms the basis for neuronal circuit complexity and can determine differences between otherwise similar circuits. Although synaptic plasticity is fairly well characterized, much less is known about the molecular mechanisms underlying intrinsic plasticity, especially its transcriptional regulation. We show that the Microphthalmia-associated transcription factor (Mitf), best known as the master regulator of melanocytic cell fate and differentiation, plays a central role in homeostatic intrinsic plasticity of olfactory bulb (OB) projection neurons. Mitral and tufted (M/T) neurons from Mitf mutant mice are hyperexcitable due to reduced Type-A potassium current (IA) and they exhibit reduced expression of Kcnd3, which encodes a potassium voltage-gated channel subunit (Kv4.3) important for generating the IA. Furthermore, expression of the Mitf and Kcnd3 genes is activity-dependent in OB projection neurons, The MITF protein binds to and activates expression from Kcnd3 regulatory elements. Activity can therefore affect Kcnd3 expression directly via MITF. Moreover, Mitf mutant mice have changes in olfactory habituation and have increased habitutation for an odourant following long-term exposure, indicating that regulation of Kcnd3 is pivotal for long-term olfactory adaptation. Our findings show that Mitf acts as a direct regulator of intrinsic homeostatic feedback, plays a key role in olfactory adaptation and links neuronal activity, transcriptional changes and neuronal function. Significance statementA direct, Mitf-dependent link between neuronal activity and homeostatic changes in the expression of a key potassium channel subunit is demonstrated in projection neurons of the mouse OB. This is one of the first studies that directly link activity and genetically defined changes in intrinsic plasticity, leading to changes in neuronal response. These findings broaden the general understanding of transcriptional regulation of homeostatic intrinsic plasticity in learning and memory. The results are also important for understanding the role of Mitf in other cell types. Regulation of intrinsic plasticity has wide-ranging implications and fundamental importance for neurological diseases such as neurodegeneration, autism and epilepsy.

neuroscience↗