Neurotrophic Factor Receptors in Epiretinal Membranes After Human Diabetic Retinopathy
- Takayuki Harada, MD, PHD12,
- Chikako Harada, MD, PHD12,
- Yoshinori Mitamura, MD, PHD34,
- Chihiro Akazawa, MD, PHD5,
- Kenji Ohtsuka, MD, PHD4,
- Shigeaki Ohno, MD, PHD2,
- Shinobu Takeuchi, MD, PHD3 and
- Keiji Wada, MD, PHD1
- 1Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
- 2Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
- 3Toho University Sakura Hospital, Sakura, Chiba, Japan
- 4Sapporo Medical University, Sapporo, Hokkaido, Japan
- 5Department of Neurochemistry, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
Abstract
OBJECTIVE—Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions, including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to determine whether neurotrophic factor receptors (tyrosine kinase receptors trkA, trkB, and trkC; low-affinity neurotrophin [NT] receptor p75 [p75NTR]; glial cell line–derived neurotrophic factor receptor-α1 [GFRα1] and GFRα2; and Ret) are involved in the formation of ERMs after PDR.
RESEARCH DESIGN AND METHODS—ERM samples were obtained by vitrectomy from 19 subjects with PDR aged 57 ± 8 years with 17 ± 8 years of diabetes and 15 subjects with idiopathic ERM. They were processed for RT-PCR analysis. In addition, 11 ERM samples from PDR patients aged 47 ± 18 years with 13 ± 4 years of diabetes were processed for immunohistochemical analysis.
RESULTS—Expressions of trkA, trkB, trkC, p75NTR, and Ret mRNAs were similar in both groups. In contrast, GFRα2 expression levels were significantly higher (17 of 19 vs. 2 of 15 subjects in idiopathic ERM, P < 0.0001) in PDR subjects. Accordingly, immunohistochemical analysis revealed expression of GFRα2 protein in all of the 11 ERMs derived from PDR patients, and that region was double-labeled with glial cell-specific markers. On the other hand, GFRα1 expression was lower (8 of 19 vs. 12 of 15 subjects with idiopathic ERM, P = 0.0258) in PDR subjects.
CONCLUSIONS—These results suggest a possibility that glial cell line-derived neurotrophic factor receptor (GDNF) subtypes are differently involved in the formation of ERMs.
- bFGF, basic fibroblast growth factor
- CNS, central nervous system
- ERM, epiretinal membrane
- GFR
- glial cell line–derived neurotrophic factor receptor
- GDNF, glial cell line–derived neurotrophic factor
- G3PDH, glyceraldehyde-3-phosphate dehydrogenase
- NGF, nerve growth factor
- NT, neurotrophin
- NTN, neurturin
- p75NTR, low-affinity NT receptor p75
- PDR, proliferative diabetic retinopathy
- PVR, proliferative vitreoretinopathy
- TGF-β, transforming growth factor-β
- trk, tyrosine kinase receptor.
Footnotes
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Address correspondence and reprint requests to Takayuki Harada, MD, PhD, Department of Molecular Neuroscience, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. E-mail: harada.aud{at}mri.tmd.ac.jp.
Received for publication 3 November 2001 and accepted in revised form 13 March 2002.
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