Mitochondria are essential for neurons and must be optimally distributed along their axon to fulfil local functions. A high density of mitochondria has been observed in retinal ganglion cell (RGC) axons of an unmyelinated region of the optic nerve, called the glial lamina (GL) in mouse (lamina cribrosa in human). In glaucoma, the world’s leading cause of irreversible blindness, the GL is the epicenter of RGC degeneration and is connected to mitochondrial dysfunction. It is generally accepted that the local accumulation of mitochondria in the GL is established due to the higher energy requirement of unmyelinated axons. Here we revisit the connection between mitochondrial positioning and myelin in RGC axons. We show that the high density of mitochondria in the GL is restricted to larger axons and is established before myelination. Thus, contrary to a longstanding belief in the field, the myelination pattern is not responsible for the establishment of the local accumulation of mitochondria in GL axons. Our findings open new research avenues likely critical to understanding the pathophysiology of glaucoma.

中文翻译：

---

视神经胶质层中轴突线粒体的局部积累先于髓鞘形成

线粒体对神经元至关重要，必须沿其轴突最佳分布以实现局部功能。在小鼠（人的筛板）称为神经胶质层（GL）的视神经无髓鞘区域的视网膜神经节细胞（RGC）轴突中观察到高密度的线粒体。在青光眼（世界上导致不可逆失明的主要原因）中，GL 是 RGC 退化的中心，并与线粒体功能障碍有关。人们普遍认为，GL 中线粒体的局部积累是由于无髓轴突的更高能量需求而建立的。在这里，我们重新审视了 RGC 轴突中线粒体定位和髓磷脂之间的联系。我们表明，GL 中的高密度线粒体仅限于较大的轴突，并在髓鞘形成之前建立。因此，与该领域长期以来的信念相反，髓鞘形成模式不负责在 GL 轴突中建立线粒体的局部积累。我们的发现开辟了新的研究途径，可能对了解青光眼的病理生理学至关重要。