Mitochondrial DNA Variations in Primary Congenital Glaucoma

Abstract

Purpose: : To screen mitochondrial genome for nucleotide changes in Primary congenital glaucoma (PCG).

Methods: : Patients with PCG presenting within 1 year of birth were included. There were 30 males and 4 females. The entire coding region of the mitochondrial genome was amplified by Polymerase Chain Reaction (PCR) in 34 PCG patients and 50 healthy controls. The whole mitochondrial genome except D-loop was sequenced. All sequences were analyzed against mitochondrial sequence NC_012920.

Results: : Mitochondrial DNA sequencing revealed 133 nucleotide variations in PCG patients and 57 in controls respectively. Out of 133 variations in PCG, 32 changes were novel. We identified 67 (50.37%) variations in complex I, 12 (9.02%) in complex III, 26 (19.54%) in complex IV and 23 (17.29%) in complex V. Out of total variations reported, complex I had 25 (37.8%), complex III had 3 (25%), complex IV had 7 (26.9%) and complex V had 11(47.82%) non-synonymous base changes respectively.

Conclusions: : PCG patients show a high number of Mitochondrial DNA variations. Mutations in mitochondrial genes regulating oxidative phosphorylation may result in decreased ATP and supra-physiological ROS (reactive oxygen species) levels. The resultant oxidative stress may impair development and differentiation of trabecular meshwork and result in trabecular dysgenesis.

Keywords: mitochondria • genetics • oxidation/oxidative or free radical damage