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WEN LI, Jianbo He, Changhua Ye, Hu Huang; The roles of chemokine receptors CXCR5 in retinal ischemia. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4684.
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© ARVO (1962-2015); The Authors (2016-present)
Damage to retina by ischemia is common in eye disorders, such as glaucoma, retinopathy of prematurity (ROP), and diabetic retinopathy (DR). However, the underlying mechanisms are poorly understood. In this study, we investigated the roles of chemokine receptor CXCR5 in the pathological process of retinal ischemia in an ischemia-reperfusion (I-R) model.
Retinal I-R was induced in the 4~6-week-old CXCR5 knockout (KO) mice and the age-matched C57BL6/J wild type (WT) mice by raising intraocular pressure to 80-90 mmHg for 90 min followed by restoration of normal pressure. At 2 and 7 days after I-R surgery, the mice were sacrificed and the eyes were harvested for further analyses. Infiltrated leukocytes were quantified on the H&E stained cryo-sections. Capillary degeneration was determined on the intact retinal vasculatures prepared by trypsin digestion. Apoptotic cell death was measured by active caspase-3 staining. The NeuN immune-positive (+) cells were used to quantify ganglion cells. The Iba1(+) cells were used to detect retinal microglia. The protein expression and cellular localization of zonula occludens (ZO)-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were examined by Western blots (WB), immunofluorescence staining and confocal microscopy.
Retinal I-R increased the immunoreactivity of ICAM-1 and VCAM-1 throughout the retina, including photoreceptors, outer plexiform layer, inner plexiform layer and ganglion cell layer, in both KO and WT mice. The infiltrated leukocytes were observed largely at 2 days after I-R injury, but no or little at 7 days; and the number of infiltrated cells (most likely neutrophils) was greater in CXCR5 KO mice than WT mice. WB results showed that CXCR5 deficiency led to greater protein degradation of the tight junction ZO-1 caused by I-R injury in KO mice, compared to WT mice. The apoptotic death of ganglion cells, vascular cells and retinal neurons was also increased in the KO mice.
Our results suggest that CXCR5 deficiency causes the impairment of inflammatory cells trafficking from/to the eye, which leads to the accumulation of infiltrated leukocytes and accelerated damage to retina, in the retinal I-R model.
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