Neurotrophic Factor Receptors in Epiretinal Membranes After Human Diabetic Retinopathy.
Harada, Takayuki MD, PHD 1,2; Harada, Chikako MD, PHD 1,2; Mitamura, Yoshinori MD, PHD 3,4; Akazawa, Chihiro MD, PHD 5; Ohtsuka, Kenji MD, PHD 4; Ohno, Shigeaki MD, PHD 2; Takeuchi, Shinobu MD, PHD 3; Wada, Keiji MD, PHD 1
[Article] Diabetes Care. 25(6):1060-1065, June 2002.

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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-[alpha]1 [GFR[alpha]1] and GFR[alpha]2; 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, GFR[alpha]2 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 GFR[alpha]2 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, GFR[alpha]1 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.

(C) 2002 by the American Diabetes Association, Inc.