Insulin-like growth factor-I and its receptor in neovascular age-related macular degeneration.
OBJECTIVE
The insulin-like growth factor (IGF)-I protein is a growth-promoting polypeptide that can act as an angiogenic agent in the eye. The purpose of the current study was to localize the expression of IGF-I and its receptor (IGF-IR) mRNA and IGF-IR protein in situ in the normal human eye and to examine the presence of expression in eyes with neovascular age-related macular degeneration (AMD).


METHODS
Formalin-fixed, paraffin-embedded slides of 4 normal control eyes and 14 eyes with choroidal neovascularization (CNV) secondary to AMD were examined. Three eyes with proliferative diabetic retinopathy were studied as the positive control. IGF-I and IGF-IR mRNA was detected by in situ hybridization with digoxigenin-labeled RNA probes. IGF-IR protein was studied by immunohistochemistry.


RESULTS
In the normal retina, IGF-I and IGF-IR mRNA expression was found throughout the neuroretinal layers, in the retinal pigment epithelium (RPE), and in some choriocapillary and retinal capillary endothelial cells. In eyes with CNV we found IGF and IGF-IR mRNA in capillary endothelial cells, some transdifferentiated RPE, and fibroblast-like cells. IGF-IR protein was found in normal eyes in all neuroretinal layers, in the RPE, and in the choroidal vessels. In eyes with CNV, IGF-IR protein was present in the RPE monolayer, in transdifferentiated RPE, and in newly formed vessels.


CONCLUSIONS
The colocalization of protein and receptor indicates an autocrine function of IGF-I in the normal human retina. Because IGF-I participates in ocular neovascularization, synthesis of IGF-IR and IGF-I in endothelial cells, RPE cells, and fibroblast-like cells in CNV may point toward a role for this growth factor in the pathogenesis of neovascular AMD.
Lambooij
Antoinette C
AC
Department of Ophthalmology, Erasmus Medical Center Rotterdam, The Netherlands. a.lambooij@erasmusmc.nl
van Wely
Karel H M
KH
Lindenbergh-Kortleve
Dicky J
DJ
Kuijpers
Robert W A M
RW
Kliffen
Mike
M
Mooy
Cornelia M
CM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002829:Choroid / Q000098:blood supply; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008268:Macular Degeneration / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism
D015347:RNA Probes; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1