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Despoina Gkotsi, Gerassimos Lascaratos, David Chau, Anthony Schapira, David F Garway-Heath; Mitochondrial contribution to the resistance to glaucoma in ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3659.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously reported (ARVO 2013) that ocular hypertension (OHT) patients, resistant to glaucomatous damage, show increased mitochondrial function in peripheral blood lymphocytes compared to age-similar non-glaucomatous subjects and patients with progressing normal tension glaucoma (NTG). We hypothesise that enhanced mitochondrial function confers resistance to glaucoma progression.<br /> 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, and also by measuring mitochondrial DNA (mtDNA) levels.
Peripheral blood lymphocytes were collected from: 15 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. Complementary DNA (cDNA) was synthesised following RNA isolation, and was used to quantify a panel of messenger RNAs (mRNAs) contributing to mitochondrial function and structure, such as optic atrophy 1 (OPA1) and citrate synthase (CS), using the SYBR green-based qPCR. Beta-actin was amplified to control the mRNA loadings. Additionally, total DNA was prepared. SYBR green-based qPCR was used to amplify the D-loop region of the mtDNA, and the nuclear B2M gene. mtDNA level was expressed relative to the nuclear DNA level. The Mann Whitney U Test was used to compare groups (SPSS 22.0).
The transcript and relative mtDNA levels are shown in the Table. OPA1 and CS that are related to mitochondrial morphology and content, respectively, had higher transcript levels in OHT patients. mtDNA levels were also higher in OHT patients.
The results suggest high abundance of proteins linked to mitochondrial elongation and mitochondrial content, and increased mtDNA levels are associated with resistant OHT.
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