Abstract
Microglial activation is associated with glaucoma. In the model of unilateral laser-induced ocular hypertension (OHT), the time point at which the inflammatory process peaks remains unknown. Different time points (1, 3, 5, 8, and 15 d) were compared to analyze signs of microglial activation both in OHT and contralateral eyes. In both eyes, microglial activation was detected in all retinal layers at all time points analyzed, including: i) increase in the cell number in the outer segment photoreceptor layer and plexiform layers (only in OHT eyes) from 3 d onward; ii) increase in soma size from 1 d onward; iii) retraction of the processes from 1 d in OHT eyes and 3 d in contralateral eyes; iv) increase in the area of the retina occupied by Iba-1+ cells in the nerve fiber layer/ganglion cell layer from 1 d onward; v) increase in the number of vertical processes from 1 d in contralateral eyes and 3 d in OHT eyes. In OHT eyes at 24 h and 15 d, most Iba-1+ cells were P2RY12+ and were down-regulated at 3 and 5 d. In both eyes, microglial activation was stronger at 3 and 5 d (inflammation peaked in this model). These time points could be useful to identify factors implicated in the inflammatory process.
Highlights
We identified microglia based on the expression of Iba-1 and P2RY12, allowing us to distinguish resident microglia from cells derived from infiltrating monocytes or macrophages during glaucoma-induced inflammation
These parameters were measured at various times after unilateral laser induction of ocular hypertension (OHT)
This work is, to the best of our knowledge, the first comparative study of microglial activation among different time points (1, 3, 5, 8 and 15 days) after unilateral laser induction of OHT in an experimental mouse model. It is the first study of this OHT mouse model in which P2RY12 expression is analyzed over time in retinal whole-mounts
Summary
In OHT eyes at 24 h and 15 d, most Iba-1+ cells were P2RY12+ and were down-regulated at 3 and 5 d In both eyes, microglial activation was stronger at 3 and 5 d (inflammation peaked in this model). Risk factors for glaucoma include elevated IOP4, vascular dysfunction, oxidative stress and immune-related neuroinflammation[5,6,7,8,9,10] Another contributing factor is microglial activation, which helps drive inflammation that contributes to loss of retinal ganglion cells[11]. Activated microglia cells densely extend their processes toward the lesion site within a few minutes[22,23], or they migrate to the site of damage[24,25] to prevent lesion spread These first responses are mediated by metabotropic purinergic P2Y12 receptors, which are stimulated by ATP released from dead or injured neurons[22,23].
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