Low content of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor predicts progression of diabetic retinopathy

被引:127
作者
Boehm, BO
Lang, G
Volpert, O
Jehle, PM
Kurkhaus, A
Rosinger, S
Lang, GK
Bouck, N
机构
[1] Univ Ulm, Sch Med, Dept Internal Med, Div Endocrinol & Diabet, D-89081 Ulm, Germany
[2] Univ Ulm, Sch Med, Dept Ophthalmol, D-89081 Ulm, Germany
[3] Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA
[4] Northwestern Univ, Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
[5] Northwestern Univ, Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA
关键词
angiogenesis; angiogenic inhibitors; aqueous humor; diabetic retinopathy; pigment epithelium-derived factor (PEDF); vascular endothelial growth factor (VEGF);
D O I
10.1007/s00125-003-1040-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis. Retinopathy is the most common microvascular complication of diabetes. Our aim was to address the predictive value of pro-angiogenic and anti-angiogenic markers for progression of retinopathy. Methods. Aqueous humor was collected at cataract surgery from 32 diabetic patients who had no or very mild retinopathy (ETDRS stage less than or equal to20) and 33 normoglycaemic control subjects. Content of pro-angiogenic vascular endothelial growth factor and angiogenic inhibitor pigment epithelium-derived factor were determined. Angiogenic activity was quantified by measuring its effect on the migration of capillary endothelial cells. The predictive value of the initial level of these markers for progression of retinopathy was studied by following the probands for a maximum of 75 months. Results. In the aqueous fluid content of vascular endothelial growth factor was increased in diabetic patients (mean values 492 versus 292 pg/ml; p=0.0052), and pigment epithelium-derived factor values were decreased (mean values 1740 versus 3680 ng/ml; p=0.0058) compared to control subjects. Of the diabetic patients ten progressed during follow-up (ETDRS stage >47B). This subgroup showed lower pigment epithelium-derived factor content when compared to non-progressors and control subjects. Migratory activity in samples of patients from the control group and in diabetic patients without progression was generally inhibitory due to pigment epithelium-derived factor. Inhibition was blocked by neutralizing antibodies to pigment epithelium-derived factor. In diabetic patients initial angiogenic activity was higher in those who later developed retinopathy (vs. controls p=0.00005; vs. no progressors p=0.0003). Both pigment epithelium-derived factor and migratory response predicted progression. Conclusion/Interpretation. Pigment epithelium-derived factor is an important negative regulator of angiogenic activity of aqueous humor. Its content in the aqueous humor of diabetic patients strongly predicts who among them will develop progression of retinopathy.
引用
收藏
页码:394 / 400
页数:7
相关论文
共 35 条
[1]   INCREASED VASCULAR ENDOTHELIAL GROWTH-FACTOR LEVELS IN THE VITREOUS OF EYES WITH PROLIFERATIVE DIABETIC-RETINOPATHY [J].
ADAMIS, AP ;
MILLER, JW ;
BERNAL, MT ;
DAMICO, DJ ;
FOLKMAN, J ;
YEO, TK ;
YEO, KT .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 1994, 118 (04) :445-450
[2]   SUPPRESSION OF RETINAL NEOVASCULARIZATION IN-VIVO BY INHIBITION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) USING SOLUBLE VEGF-RECEPTOR CHIMERIC PROTEINS [J].
AIELLO, LP ;
PIERCE, EA ;
FOLEY, ED ;
TAKAGI, H ;
CHEN, H ;
RIDDLE, L ;
FERRARA, N ;
KING, GL ;
SMITH, LEH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (23) :10457-10461
[3]   VASCULAR ENDOTHELIAL GROWTH-FACTOR IN OCULAR FLUID OF PATIENTS WITH DIABETIC-RETINOPATHY AND OTHER RETINAL DISORDERS [J].
AIELLO, LP ;
AVERY, RL ;
ARRIGG, PG ;
KEYT, BA ;
JAMPEL, HD ;
SHAH, ST ;
PASQUALE, LR ;
THIEME, H ;
IWAMOTO, MA ;
PARK, JE ;
NGUYEN, HV ;
AIELLO, LM ;
FERRARA, N ;
KING, GL .
NEW ENGLAND JOURNAL OF MEDICINE, 1994, 331 (22) :1480-1487
[4]  
Becerra SP, 1997, ADV EXP MED BIOL, V425, P223
[5]   Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration [J].
Bilak, MM ;
Corse, AM ;
Bilak, SR ;
Lehar, M ;
Tombran-Tink, J ;
Kuncl, RW .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1999, 58 (07) :719-728
[6]   Octreotide reduces vitreous hemorrhage and loss of visual acuity risk in patients with high-risk proliferative diabetic retinopathy [J].
Boehm, BO ;
Lang, GK ;
Jehle, PM ;
Feldmann, B ;
Lang, GE .
HORMONE AND METABOLIC RESEARCH, 2001, 33 (05) :300-306
[7]   How tumors become angiogenic [J].
Bouck, N ;
Stellmach, V ;
Hsu, SC .
ADVANCES IN CANCER RESEARCH, VOL 69, 1996, 69 :135-174
[8]   PEDF: anti-angiogenic guardian of ocular function [J].
Bouck, N .
TRENDS IN MOLECULAR MEDICINE, 2002, 8 (07) :330-334
[9]  
Cao W, 2001, INVEST OPHTH VIS SCI, V42, P1646
[10]   Pigment epithelium-derived factor delays the death of photoreceptors in mouse models of inherited retinal degenerations [J].
Cayouette, M ;
Smith, SB ;
Becerra, SP ;
Gravel, C .
NEUROBIOLOGY OF DISEASE, 1999, 6 (06) :523-532