Abstract
Purpose :
The Lamina Cribrosa (LC) region of the optic nerve is an important site of damage in glaucoma. AMP-activated protein kinase (AMPK) is the main sensor of cellular energy status in virtually all cells, and is highly conserved across all eukaryotic species. AMPK is upregulated in both cancer and fibrosis. AMPK is activated in response to energy stress by sensing increases in AMP: ATP and ADP: ATP ratios. Here, we investigate the expression of an isoform of AMPK in normal and glaucoma LC cells and examine the possible effect of AMPK on pro-fibrotic gene expression found in glaucoma LC cells.
Methods :
LC cells were obtained and cultured from 2 normal non-glaucomatous and 2 confirmed glaucoma age matched eye donors. Expression of an AMPK isoform was measured in both normal and glaucoma LC cells using Quantitative Real Time Polymerase Chain Reaction (qPCR).
Results :
The expression level of the AMPK isoform was found to be significantly enhanced in glaucoma LC cells compared to normal control LC cells (1.23 ± 0.083 in glaucoma LC cells versus 0.86 ± 0.067 in normal LC cells; p<0.05; n=2). The relative expression of AMPK was calculated using △△Ct method, after being normalized to the housekeeping ribosomal gene 18S.
Conclusions :
The data shows that AMPK is significantly elevated in glaucoma LC cells versus normal LC cells. This suggests a role for AMPK as a key driver of underlying fibrotic changes in glaucomatous LC cells, leading to increased proliferation, reduced apoptosis and augmented metabolism. Blockade of AMPK appears to be critically associated with this process of metabolism. Halting the pro-fibrotic activity and metabolism of glaucoma LC cells by restoring AMPK expression and activity to normal levels may lead to a new therapeutic approach targeted at reducing fibrosis in glaucoma. We anticipate that this novel therapeutic approach could ameliorate the ongoing optic nerve cupping, thereby enhancing long-term patient outcomes and quality of life in glaucoma.
This is a 2021 ARVO Annual Meeting abstract.