Overexpression of nuclear transport factor 2 may protect against diabetic retinopathy.
OBJECTIVE
We performed human, animal, and in vitro studies to examine the potential role of nuclear transport factor 2 (NTF2) in conferring resistance to diabetic retinopathy (DR).


METHODS
Blood NTF2 levels were assessed in two groups of patients with type 2 diabetes mellitus. Group P patients had a history of proliferative DR (PDR), while group N patients did not. The retinal vasculature was examined in diabetic rats three months after they received an intravitreal injection of a recombinant adeno-associated virus (rAAV) vector overexpressing NTF2 (rAAV2-NTF2). Control rats were treated with rAAV2 only. Rat retinal capillary endothelial cells (RRCECs) were infected with rAAV2-NTF2, or with a vector expressing siRNA targeted against NTF2, to assess the effects of overexpression and inhibition of NTF2 on vascular endothelial growth factor (VEGF) expression (mRNA and protein).


RESULTS
There was a strong trend for patients with DR to have lower blood NTF2 levels compared to those who did not have DR (0.10+/-0.01 versus 0.20+/-0.08, p=0.079). There was significantly less retinal blood vessel leakage in diabetic rats infected with rAAV2-NTF2 compared to controls (16.5+/-2.9 versus 24.7+/-7.3, p=0.039). These rats exhibited normal retinal vasculature and blood-retinal barrier function. VEGF expression was inhibited by NTF2 overexpression and stimulated by NTF2 inhibition, (protein [0.41+/-0.05 versus 0.23+/-0.06] and mRNA [0.37+/-0.04 versus 0.23+/-0.06] p<0.01 for all).


CONCLUSIONS
These finding suggest that NTF2 is a potential mediator of retinal vasculature integrity. NTF2 may act by altering VEGF expression, thereby influencing the development of DR in patients with diabetes mellitus.
Li
Bin
B
Key Laboratory of Ophthalmology of the Ministry of Education and Zhong-Shan Ophthalmic Center, Sun Yet-Sun University, Guangzhou City, People's Republic of China.
Zhang
Hai-Qing
HQ
Shi
Yu
Y
Min
Yun-Bing
YB
Lin
Shao-Fen
SF
Wu
Kai-Li
KL
Hu
Jie
J
Tang
Shi-Bo
SB
D000368:Aged; D000818:Animals; D003930:Diabetic Retinopathy / Q000235:genetics / Q000517:prevention & control*; D042783:Endothelial Cells / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
C038965:NUTF2 protein, human; D029543:Nucleocytoplasmic Transport Proteins; C503612:Nutf2 protein, rat; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016650:Fluorescein-5-isothiocyanate