Lateral habenular nucleus lesions improve dry eye symptoms in type 2 diabetic rats

Figure 1. T2DM rat model induced by HFSD.A. HFSD combined with streptozotocin resulted in a significant increase in FSG levels in rats. There was no significant change in blood glucose levels in control rats.B. HbA1c levels were significantly higher in T2DM rats than in controls.C. Insulin levels were significantly higher in T2DM rats than in controls.Ctrl: control; T2DM: type 2 diabetes; FSG: fast serum glucose; HbA1c: Glycated Hemoglobin A1c; INS: insulin; *p<0.05; ***p<0.001.Figure 2. Significant DES were observed in rats with T2DM.A. Tear secretion was significantly reduced in T2DM rats after HFSD induction. There was no significant change in the control group before and after induction. Tear secretion in T2DM rats was considerably lower than that in the control.B. After HFSD induction, TBUT in T2DM rats was significantly shorter and significantly less than control.C. After HFSD induction, the IOP of the rats increased significantly. The IOP of the T2DM rats was considerably higher than that of the control.Ctrl: control; T2DM: type 2 diabetes; **p<0.01; ***p<0.001.Figure 3. Bilateral LHb lesions reduce blood glucose and improve DES in T2DM rats.A. Bilateral LHb lesions significantly decreased blood glucose in T2DM rats. There was no significant change in blood glucose levels in T2DM+sham rats.B. LHb lesions lead to increased tear secretion in T2DM rats.C. LHb lesions prolonged tear film rupture in T2DM rats.D. LHb lesions reduce IOP in T2DM rats.FSG: fast serum glucose; **p<0.01; ***p<0.001.Figure 4. LHb lesions downregulate PROX-1 and LYVE-1 expression in corneal limbus and conjunctiva.A. Representative Western blot bands of the corneal limbus.B. Representative Western blot bands of the conjunctiva.C. The LYVE-1 expression in corneal limbus. LYVE-1 expression was found to be significantly increased in the corneal limbus of T2DM rats. LHb lesions resulted in a decrease in LYVE-1 expression in the corneal limbus of T2DM rats.D. The LYVE-1 expression in conjunctiva. LYVE-1 expression was increased in the conjunctiva of T2DM rats. LHb lesions could decrease LYVE-1 expression in the conjunctiva of T2DM rats.E. The PROX-1 expression in corneal limbus. PROX-1 expression was increased in the corneal limbus of T2DM rats. LHb lesions lead to a decrease in PROX-1 expression in the corneal limbus of T2DM rats.F. The PROX-1 expression in conjunctiva. PROX-1 expression was increased in the conjunctiva of T2DM rats. LHb lesions lead to a decrease in PROX-1 expression in the conjunctiva of T2DM rats.LYVE-1: Lymphatic vessel endothelial hyaluronan receptor-1; PROX-1: Prospero homeobox protein 1; Ctrl: control; T2DM: type 2 diabetes; N.S.: no significant difference; *p<0.05; **p<0.01; ***p<0.001.