The iron carrier transferrin is upregulated in retinas from patients with age-related macular degeneration.
OBJECTIVE
Iron can cause oxidative stress, and elevated iron levels have been associated with several neurodegenerative diseases including age-related macular degeneration (AMD). Transferrin, an iron transport protein, is expressed at high levels in the retina. The purpose of this study was to assess transferrin involvement in AMD by determining the expression profile of transferrin in retinas with AMD compared with retinas without evidence of disease.


METHODS
Postmortem retinas were obtained from AMD and non-AMD eyes. Expression of transferrin was assessed in a microarray dataset from 33 retinas of unaffected donors and 12 retinas of patients with AMD (six with neovascular AMD and six with non-neovascular AMD). Quantitative real-time RT-PCR (QPCR) was used to confirm the microarray results. Transferrin protein expression was assessed by semiquantitative Western blot analysis and immunohistochemistry.


RESULTS
In comparison to unaffected retinas, mean transferrin mRNA levels, as measured by microarray analysis were elevated 3.5- and 2.1-fold in non-neovascular and neovascular AMD retinas, respectively. Semiquantitative Western blot analysis demonstrated a 2.1-fold increase in transferrin protein in AMD eyes. Immunohistochemistry showed more intense and widespread transferrin label in AMD maculas, particularly in large drusen, Müller cells, and photoreceptors.


CONCLUSIONS
These data demonstrate that transferrin expression is increased in the retinas of patients with AMD relative to those of healthy control patients of comparable age. Along with previous studies that have demonstrated elevated iron levels in AMD retinas, early onset drusen formation in a patient with retinal iron overload resulting from aceruloplasminemia, and retinal degeneration with some features of macular degeneration in the iron-overloaded retinas of ceruloplasmin/hephestin knockout mice, the present study suggests that altered iron homeostasis is associated with AMD.
Chowers
Itay
I
Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Wong
Robert
R
Dentchev
Tzvete
T
Farkas
Ronald H
RH
Iacovelli
Jared
J
Gunatilaka
Tushara L
TL
Medeiros
Nancy E
NE
Presley
J Brett
JB
Campochiaro
Peter A
PA
Curcio
Christine A
CA
Dunaief
Joshua L
JL
Zack
Donald J
DJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014168:Transferrin / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
D012333:RNA, Messenger; D014168:Transferrin