Objective      To investigate the internalization and lysosomal degradation of retinal aquaporin-4 (AQP4) induced by different reperfusion phases after acute ocular hypertension (AOH) in rats

so as to explore the relationship of AQP4 internalization and degradation with the glial edema of retinae.       Methods      A total o

f 72 rats

8-week-old

and weighting 190 to 210 g

were induced to AOH models in the left eye

and then divided into 6 reperfusion groups (n=12 for each group) according to the different duration of reperfusion

that is

0

1

2

4

8 and 12 h following 60 minutes’ ischemia. Double-immunofluorescence labeling was applied to identify the localization of glial cells and detect the co-expression of AQP4/early endosome antigen 1 (EEA1)

AQP4/mannose-6-phosphate receptor (MPR)

and AQP4/lysosomal-associated membrane protein-1 (LAMP1). The numbers of single-labeled AQP4

+

cells

and double-labeled AQP4

+

/EEA1

+

  and AQP4

+

/LAMP1

+

cells were estimated and statistical compared between the consecutive groups.       Results      The astrocytes which were positive to GFAP were located in the nerve fiber layer and ganglion cell layer

and the Muller cells positive to GS were located in the inner nuclear layer. AQP4/EEA1 and AQP4/MPR were co-localized during an 8-hour reperfusion window following 60 min  ischemia

but only AQP4 and EEA1 were still observed till 12 h of reperfusion. The co-expression of AQP4 and LAMP1 was seen from 1 to 12 h of reperfusion

with increased first and then decreased gradually

At the 4-hour reperfusion

the cells co-expressing AQP4 and LAMP1 reached the largest count

  accounting for (55.60±13.03)% (

P

0.05

compared with other time points).       Conclusion      Ischemia-reperfusion injury in the retina resulted from ocular hypertension induces the internalization of retinal AQP4

which are then degraded by lysosome. Internalization and lysosomal degradation of AQP4 may play a role in the pathogenesis and progress of retinal edema.