Abstract
Purpose :
To determine whether short-term reduction of cerebrospinal fluid pressure (CSFp) triggers selective mitochondrial autophagy and ultrastructural changes in Sprague Dawley(SD) rat.
Methods :
The experiment included 26 male SD rats, during which underwent continuous cerebrospinal fluid drainage for 6 hours (n=13). For control, 13 normal rats were anaesthetized for 6 hours. We used transmission electron microscopy (TEM) to display the ultrastructural features of mitochondria in the orbital optic nerve(ON), the retinal autophagosomes, and the retinal ganglion cells (RGCs) axons in the optic nerve head (ONH). Retinal mitophagy was detected by immunostaining and western blot for PTEN induced putative kinase 1(PINK1), Parkin, LC3B-II/I, and lysosome-associated membrane protein 1(LAMP1).
Results :
TEM showed that the area of mitochondria was much bigger, wider, and shorter in ON,
the retinal autophagosomes increased in the low-CSFp group, without loss of axons in the ONH compared with anaesthetized control. Elevation of PINK1, Parkin, and LAMP1 over time were observed in the low-ICP retinas. LC3B-II/I significantly increased only at 0day after surgery.
Conclusions :
Following short-term CSFp reduction, morphologic and functional changes of mitochondria may precede axonal loss, which may be early neuroprotective mechanism. CSFp may also be a major risk factor involving in the development of glaucoma comparable to intraocular pressure(IOP).
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.