Mitochondrial decline in the ageing old world primate retina: Little evidence for difference between the centre and periphery

Abstract

Mitochondrial decline is a key feature of ageing. The retina has more mitochondria than any other tissue and ages rapidly. To understand human retinal ageing it is critical to examine old world primates that have similar visual systems to humans, and do so across central and peripheral regions, as there is evidence for early central decline. Hence, we examine mitochondrial metrics in young and ageing Macaca fascicularis retinae. In spite of reduced ATP with age, primate mitochondrial complex activity did not decline. But mitochondrial membrane potentials were reduced significantly, and concomitantly, mitochondrial membrane permeability increased. The mitochondrial marker Tom20 declined significantly, consistent with reduced mitochondria number, while VDAC, a voltage dependent anion channel and diffusion pore associated with apoptosis increased significantly. In spite of these clear age-related changes, there was almost no evidence for regional differences between the centre and the periphery in these mitochondrial metrics. Primate cones do not die with age, but many showed marked structural decline with vacuous spaces in proximal inner segments normally occupied by endoplasmic reticulum (ER), that regulate mitochondrial autophagy. In many peripheral cones, ER was displaced by the nucleus that transposed across the outer limiting membrane and could become embedded in mitochondrial populations. These data are consistent with significant changes in retinal mitochondria in old world primate ageing but provide little if any evidence that aged central mitochondria suffer more than those in the periphery.

VDAC in Retinal Health and Disease

“…The level of fragmented and degraded mitochondrial DNA (mtDNA) increases significantly [ 89 ]. Finally, the mitochondrial marker Tom20 declines, suggesting that the number of mitochondria declines with age [ 90 ]. Interestingly though, in some studies, the expression and activities of complex I, II, and III did not go down when mitochondria showed other damage, perhaps suggesting a mechanism to compensate for the damage and decline in their number [ 91 ].…”

“…Regarding VDAC expression, Western blots of the whole retinas in young and old macaques showed that while the expression of Tom20 decreased, the expression of VDAC increased with age [ 90 ]. This overexpression of VDAC per mitochondrion might contribute to apoptosis which may explain the reduction in the number of rods in old primates.…”