Several factors cause glaucoma, some
working together in an individual. An emerging concept in the development of this
disease is mitochondrial dysfunction and oxidative stress in the retinal ganglion
cells (RGC), trabecular meshwork, and the lamina cribrosa (LC) in the optic
nerve head.
Sophia Millington-Ward et al, have reported
a study to assess the effectivity of an enhanced NDI1
gene (eNdi1) as a gene-independent gene therapy for glaucoma. The therapy
is aimed at improving mitochondrial function and decreasing reactive oxygen species (ROS) in a variety of
glaucoma models.
The study involved H2O2-insulted primary
porcine LC cells (pLC cells). The control cells received eNdi1 constructs
delivered via adeno-associated viral vectors (AAV-eNdi1).
H2O2 insult significantly reduced basal oxygen
consumption rate (OCR) levels (70.6 ± 37.3% versus 100.0 ± 50.2%), maximal OCR
levels (82.7 ± 23.3% versus 118.2 ± 28.3%), and ATP production (48.6 ± 32.4%
versus 71.8 ± 37.7%), indicating that oxidative stress significantly reduces
mitochondrial function in H2O2-insulted pLC cells.
Conversely, the basal OCR, maximal OCR, and
ATP production levels were significantly higher in H2O2-insulted cells that had
received AAV eNdi1 (123.9 ± 39.4%, 137.5 ± 32.3%, and 81.5 ± 28.1%,
respectively), indicating rescue of mitochondrial function in the model.
AAV-eNdi1-treated
eyes displayed significantly improved photonegative responses compared to
control PBS-injected eyes (6.4 ± 3.3 µV and 5.0 ± 3.1 µV, respectively, p <
0.05, paired t-test; n = 25).
eNdi1 directly increases mitochondrial
function in cell models of glaucoma. Additionally, the study showed that ROS
and mitochondrial stress were reduced, while cellular health was improved.
Therefore, directly increasing
mitochondrial function is protective against the development of glaucoma and provides
significant benefits.
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