Alteration in iron metabolism during retinal degeneration in rd10 mouse.
OBJECTIVE
Altered iron metabolism was implicated in retinal and macular degeneration. This study was designed to further elucidate iron homeostasis during the course of retinal degeneration in mice.


METHODS
Retinal mRNA and protein expression of transferrin, transferrin receptor, and ceruloplasmin were evaluated during retinal degeneration in rd10 mice and chemokine receptor 2 (ccr2)-deficient mice. Retinal ferritin protein levels, ferritin-bound iron, and total iron were evaluated in rd10 mice.


RESULTS
Transferrin and ceruloplasmin mRNA levels increased between 2- and 12-fold during the course of retinal degeneration in rd10 mice compared with same-age controls (P < 0.01), whereas transferrin receptor mRNA levels increased only at the late stages of degeneration in rd10 mice (2.7-fold; P = 0.005). Transferrin mRNA also increased in retinas of aged ccr2-deficient mice (1.5-fold; P = 0.05). Transferrin and ceruloplasmin protein levels corroborated with mRNA levels changes in rd10 mice albeit at a lower magnitude. Retinal ferritin protein levels increased between 1.5-fold and 2-fold (P < 0.03) in rd10 mice, and ferritin-bound iron levels increased 1.6-fold in 3-week-old rd10 mice (P = 0.03). Three-week-old rd10 mice also had a 1.4-fold increase in total retinal iron level (P = 0.05).


CONCLUSIONS
Combined with previous reports, these data suggest that retinal degenerations are associated with altered iron homeostasis regardless of the primary insult. Given the potential of iron to generate oxidative injury, its role as a therapeutic target in retinal and macular degenerations should be evaluated.
Deleon
Efrat
E
Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Lederman
Michal
M
Berenstein
Eddy
E
Meir
Tal
T
Chevion
Mordechai
M
Chowers
Itay
I
D000818:Animals; D015153:Blotting, Western; D002570:Ceruloplasmin / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005293:Ferritins / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D020868:Gene Silencing; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2 / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014168:Transferrin / Q000235:genetics*
C515335:Ccr2 protein, mouse; D012333:RNA, Messenger; D054390:Receptors, CCR2; D011990:Receptors, Transferrin; D014168:Transferrin; D005293:Ferritins; D007501:Iron; D002570:Ceruloplasmin