Abstract: OBJECTIVE: To investigate the effects of low-level lead exposure on glucose tolerance and retinal vascular permeability in mice and explore the effects of lead on diabetic retinopathy. METHODS: A lead exposure mouse model was initiated beginning with the mother generation:four groups exposed to 0,10,100,500 mg/L lead acetate. Offspring were exposed continuously until the sacrifice time. Half of mice were sacrificed at 8 weeks age,named the 8-weeks group with 12 mice (male:female:1:1) in each exposure concentration level. The graphite furnace flame atomic absorption spectrometry was used to detect lead in blood,and the intraperitoneal glucose tolerance test was used to measure glucose tolerance. The fundus vein fluorescence angiography and retinal fundus imaging technology were used to detect the vascular permeability of retinal vessels. Real-time fluorescence quantitative polymerase chain reaction (qPCR) was used to detect transcription of tight junction-related molecules. The other half of mice were sacrificed at 20 weeks age,named the 20-week group. RESULTS: The blood lead concentrations of offspring increased with the increment of lead acetate exposure level(r_{8 week}=0.887,P < 0.05;r_{20 week}=0.972,P < 0.05). The blood lead levels were higher in the 8-week than the 20-week groups when the lead acetate exposure levels were 0,10,100 mg/L. However,the 20-week group had higher blood lead than the 8-week group when the exposure was at the 500 mg/L lead acetate exposure level (P < 0.01). Compared with the control group,the blood glucose of the exposed offspring was higher within 2 hours after intraperitoneal injection of glucose,and the area under the curve of blood glucose was higher than the control mice (P < 0.05 or P < 0.01). In the 8-week group,the blood glucose and AUC of mice exposed to 10 mg/L lead acetate showed the most significantly changes compare to the controls while those at the 20-week group was at 100 mg/L. In the 8-week group,there was no vascular leakage,but only at the molecular level,the transcriptional levels of Zona occludens protein-1(ZO-1),Occludin,Claudin-1,3,5 were increased initially and then inhibited compared with control group (P < 0.05 or P < 0.01). In the 20-week group,leakages occurred in the retinal vessels of offspring exposed to lead acetate in the 100 and 500 mg/L groups,while tight junction related molecules ZO-1,Occludin,Claudin-1,3,5 transcriptions were inhibited (P < 0.01). CONCLUSION: Lead exposure increased blood glucose in the glucose tolerance test and the dose was very low before adulthood. Persistent lead exposure directly caused leakage in the retinal blood vessels which may be a potential risk factor for diseases such as diabetic retinopathy.

Key words: lead acetate, glucose tolerance, blood retinal barrier, leakage, diabetic retinopathy