Mitochondrial abnormalities in ageing macular photoreceptors.
OBJECTIVE
To evaluate somatic mitochondrial (mt)DNA mutations in the macula during ageing.


METHODS
Ten 30-microm cryostat sections from the macula (foveal and perifoveal regions) and peripheral retina of 14 donors (aged 14-94 years) were cut for cytochrome c oxidase cytochemistry. The photoreceptor layer was microdissected and DNA extracted for 4977-bp mtDNA (mtDNA(4977)) quantification using PCR. Dual cytochemistry for cytochrome c oxidase and succinate dehydrogenase allowed the detection of cytochrome c oxidase-deficient cones.


RESULTS
Findings showed a progressive accumulation of mtDNA(4977) from ages 14 to 94 years. From ages 14 to 60 years there was an increase from 0.006% to 0.25%, and from ages 60 to 94 years there was a steeper increase from 0.25% to 5.39%. Counts of cones in the dual-reacted preparations showed more cytochrome c oxidase-deficient cones in the foveal region than elsewhere.


CONCLUSIONS
The results show that mitochondrial DNA deletions and cytochrome c oxidase-deficient cones accumulate in the ageing retina, particularly in the foveal region. These defects may contribute to the changes in macular function observed in ageing and age-related maculopathy.
Barron
M J
MJ
School of Neurosciences and Psychiatry, University of Newcastle-upon-Tyne, UK.
Johnson
M A
MA
Andrews
R M
RM
Clarke
M P
MP
Griffiths
P G
PG
Bristow
E
E
He
L P
LP
Durham
S
S
Turnbull
D M
DM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002452:Cell Count; D030401:Cytochrome-c Oxidase Deficiency / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008268:Macular Degeneration / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*
D004272:DNA, Mitochondrial