Abstract
Purpose :
Increasing evidence suggests mitochondrial disorders and oxidative stress have been key contributors to the loss of retinal ganglion cells (RGCs) in glaucoma. SS-31(H-D-Arg-Dmt -Lys-Phe-NH2), a mitochondria-targeted antioxidant peptide is cell permeable and concentrated 1000-5000-fold in the inner mitochondrial membrane. This study is to investigate whether SS-31 prevents RGCs loss following the chronic ocular hypertension in rat and the underlying mechanisms.
Methods :
Magnetic microbeads was injected into the anterior chambers in SD rats to induce chronic ocular hypertension. SS-31 was intravitreally injected to test its effects on RGC survival after ocular hypertension by the counting of retrograde FG-labeled RGCs. The RGCs were isolated by the magnetic cell sorter (MACS) method for further investigating the possible mechanisms of neuroprotective effects mediated by SS-31.
ROS level and activities of mitochondrial complexes were determined using biochemical methods. Expressions of PGC-1alpha, Nrf1, Nrf2, and Tfam examined using Western blotting and Real-time quantitative PCR, respectively.
Results :
SS-31 significantly reduced RGC loss 2 and 4 weeks after ocular hypertension. The loss of RGC in PBS-(used as a negative control) and SS-31-treated retinas was approximately 35.5% and 16.8% respectively at 4weeks, compared with control. Western blot and qPCR results showed that SS-31 obviously increased the activities of mitochondrial complex I and III, and reduced ROS level in RGCs, and protein and mRNA expressions of PGC-1alpha, Nrf1, Nrf2, and Tfam were increased. Finally, we found the mitochondrial copy number increased significantly in the SS-31-treated RGCs as compared to the control eyes.
Conclusions :
The present results demonstrate that SS-31 treatment reduced the loss of RGC in an experimental model of glaucoma. SS-31 may exert neuroprotective effects by enhancing mitochondrial biogenesis, improving mitochondrial function, and reducing oxidative stress.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.