Abstract
Purpose :
Although gliotic responses are common in neurodegenerative diseases, changes in glaucoma are poorly understood. Mice heterozygous (HET) for the protein tyrosine phosphatase Meg2 (PTP-Meg2) exhibit progressive intraocular pressure (IOP) elevation, retinal ganglion cell (RGC) loss and optic nerve degeneration. Here, we analyzed oligodendroglia after chronic IOP elevation in the optic nerve of this glaucoma model.
Methods :
IOP was measured in HET and wildtype (WT) mice at 6 and 28 weeks of age (n=7/group; both sexes). Immature and mature oligodendrocytes (Olig2+) as well as mature oligodendrocytes (CC1+) were counted in optic nerve sections at 28 weeks (n=5/group). The mRNA expression levels of Pdgfra (immature oligodendrocytes), Olig2 (immature and mature oligodendrocytes), Cnp, Mbp and Plp1 (mature oligodendrocytes) were investigated via quantitative real-time-PCR (n=5-6/group). MBP and Olig2 protein levels were explored by Western blot (n=5/group). Experimental groups were analyzed by Students t-test or a pairwise fixed reallocation randomization test.
Results :
HET mice showed chronic IOP elevation at 28 weeks (p<0.001). Significantly lower numbers of CC1+ (p=0.01) and of CC1+ + Olig2+ (p=0.03) mature oligodendrocytes were found. No differences were observed in the number of Olig2+ (p=0.1) oligodendrocytes and Olig2+ + CC1- (p=0.3) oligodendrocyte precursor cells (OPCs). Expression levels of Cnp (p=0.04), Mbp (p=0.03), Olig2 (p=0.02) and Plp1 (p=0.04) were significantly reduced in the HET optic nerves. A comparable Pdgfra mRNA expression (p=0.9) was measured in WT and HET nerves. Western blot revealed lower MBP levels (p=0.04), while Olig2 levels were not altered.
Conclusions :
We verified that chronic IOP elevation is highly associated with a severe impairment of mature oligodendrocytes. This macroglia response seems to be associated with RGC loss and optic nerve damage, which was previously reported in the PTP-Meg2 glaucoma model. Interestingly, OPCs are not vulnerable to glaucomatous optic nerve degeneration.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.