Increased expression of iron-regulating genes in monkey and human glaucoma.
OBJECTIVE
To understand the mechanisms mediating retinal ganglion cell loss in glaucoma, the gene expression patterns were compared for transferrin, ceruloplasmin, and ferritin between normal and glaucomatous retina in monkey and human eyes.


METHODS
Laser photocoagulation was used to produce unilateral experimental glaucoma in monkeys. Gene expression was assessed by in situ hybridization and quantitative reverse transcription polymerase chain reaction (PCR). Immunohistochemistry was used to examine the retinal expression of iron-related proteins in the retina in experimental monkey glaucoma and human glaucoma.


RESULTS
Comparison of glaucomatous with control monkey retinas demonstrated increased mRNA expression of transferrin, ceruloplasmin, and ferritin heavy and light chains. In situ hybridization localized retinal gene expression of transferrin mainly to the inner nuclear layer and ferritin to both the inner and outer nuclear layers. Immunohistochemical examination of monkey and human glaucoma for these iron-related proteins demonstrated increases at the protein level.


CONCLUSIONS
Increased mRNA and protein levels of the iron-regulating proteins transferrin, ceruloplasmin, and ferritin are present in glaucoma. Together, these results suggest the involvement of iron and copper metabolism and associated antioxidant systems in the pathogenesis of glaucoma.
Farkas
Ronald H
RH
Guerrieri Center for Genetic Engineering and Molecular Ophthalmology, Wilmer Ophthalmological Institute, Baltimore, Maryland 21287, USA. rfarkas@jhmi.edu
Chowers
Itay
I
Hackam
Abigail S
AS
Kageyama
Masaki
M
Nickells
Robert W
RW
Otteson
Deborah C
DC
Duh
Elia J
EJ
Wang
Chenwei
C
Valenta
Danielle F
DF
Gunatilaka
Tushara L
TL
Pease
Mary E
ME
Quigley
Harry A
HA
Zack
Donald J
DJ
D000368:Aged; D000818:Animals; D002570:Ceruloplasmin / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008252:Macaca fascicularis; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014168:Transferrin / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D014168:Transferrin; D005293:Ferritins; D002570:Ceruloplasmin