Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy.
OBJECTIVE
We studied the roles of vascular endothelial growth factor (VEGF), its receptor (flt-1), advanced glycation end products (AGEs), and macrophages in the development of proliferative diabetic retinopathy.


METHODS
Ocular fluid and small specimens of iris and neovascular membrane were obtained from 30 patients who underwent vitreous surgery (19 eyes with proliferative diabetic retinopathy [PDR], 11 eyes with non-diabetic ocular diseases). VEGF and AGE levels in ocular fluid were assayed by ELISA. Immunohistochemical studies of VEGF, flt-1, AGEs, and macrophage were performed on the ocular tissues.


RESULTS
The mean VEGF and AGE levels in the vitreous (695.7pg/ml and 2.4mg/ml, respectively) were significantly higher in diabetic than in non-diabetic eyes (25.9pg/ml, p=0.0007 and 1.3mg/ml, p=0.005, respectively). Likewise, in the aqueous humor, VEGF and AGE levels were significantly higher in diabetic than in non-diabetic eyes. VEGF levels in the vitreous and aqueous humor were correlated significantly (r=0.6; p=0.02), but AGEs were not. The VEGF levels were not correlated with AGE levels in the aqueous or vitreous. In the iris, VEGF, AGEs, and macrophages were stained more prominently in the specimens from patients with diabetes than from patients without diabetes, while flt-1 staining did not differ. The Neovascular membranes were stained much more prominently for all (VEGF, flt-1, AGEs and macrophages) even when compared with the iris from patients with diabetes.


CONCLUSIONS
By analyzing aqueous and vitreous humor, proliferative membranes, and iris from the same patients, the current clinical study strongly supports previous reports that showed the role of VEGF, macrophages, and AGEs in the development of diabetic proliferative retinopathy. From the results of the current study, we showed that flt-1 plays an important role in the development of retinal neovascular membranes but the role is uncertain in the iris and retina.
Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, Omiya, Japan. kakeaki@omiya.jichi.ac.jp
Akihiro
A
Kakehashi
Shigeru
S
Inoda
Chiho
C
Mameuda
Masatoshi
M
Kuroki
Tadashi
T
Jono
Ryuji
R
Nagai
Seikoh
S
Horiuchi
Masanobu
M
Kawakami
Yasunori
Y
Kanazawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor