Insight into glaucoma damage and resistance pathways through transcript levels of genes that influence mitochondrial function and structure.

Abstract

 

Purpose

 

Preliminary results from our research team demonstrate that ocular hypertension (OHT) patients who are resistant to glaucomatous damage show better mitochondrial function in peripheral blood lymphocytes than age-similar controls and patients with progressing normal tension glaucoma (NTG). This likely indicates that enhanced mitochondrial function confers resistance to glaucoma progression. This study aims to further explore mechanisms linked to mitochondrial efficiency in OHT by measuring transcript levels of genes that influence mitochondrial function and structure.

 

Methods

 

Peripheral blood lymphocytes were collected from: 13 rapidly progressing NTG patients with low intraocular pressure (IOP, mean <16mmHg), 15 non-progressing OHT patients with mean IOP>24, and 15 age-similar healthy subjects. RNA was extracted and converted to cDNA. The mRNA levels of 22 nuclear genes affecting mitochondrial function/structure were measured using TaqMan customer-made array cards in 384-format. Beta-actin and 18S were amplified as the reference mRNA. The Mann Whitney U Test was used to compare groups (SPSS 20.0).

 

Results

 

The transcript levels are given in the Table. Aconitase 2 (ACO2), citrate synthase (CS) and optic atrophy 1 (OPA1) had higher levels in OHT patients. Glutathione peroxidase 1 (GPX1) levels were lower in OHT patients, and tumour necrosis factor alpha (TNF-α) levels were higher in both OHT and NTG patients. These genes encode Krebs cycle components (ACO2, CS), mitochondrial membrane components (OPA1), antioxidant enzymes (GPX1), and proinflammatory cytokines (TNF-a).

 

Conclusions

 

The results indicate a trend that genes involved in mitochondrial function, such as ACO2 and OPA1, have higher transcript levels in lymphocytes in the peripheral blood of OHT patients, compared to controls and NTG patients. Therefore, there seems to be a potential association between the transcript levels of genes that influence mitochondrial function/structure and mitochondrial efficiency in OHT.

 

 

Gene transcript levels (median ± IQR mRNA abundance ratio)

 

Keywords: 600 mitochondria • 533 gene/expression • 629 optic nerve