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Jacqueline Reinhard, Susanne Wiemann, Stephanie C Joachim, Andreas Faissner; Glaucomatous PTP-Meg2 deficient mice exhibit retinal protection after Latanoprost treatment. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5696.
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© ARVO (1962-2015); The Authors (2016-present)
Intraocular pressure (IOP) elevation is a main risk factor for glaucoma. In the present study we tested the response of the major anti-glaucoma drug Latanoprost, a prostaglandin analogue, in a glaucomatous PTP-Meg2 heterozygous (HET) mouse model.
IOP was evaluated by Tonolab measurements in PTP-Meg2 HET and control wildtype (WT) animals between 6 and 12 weeks of age. Following significant IOP elevation in HET mice, WT and HET animals were daily topically treated with Latanoprost (LT; 0.005% Xalatan®, Pfizer Pharmacia; n = 7-11/group) and IOP measurements were performed. Retinal ganglion cell (RGC) and microglia numbers were assessed by immunohistochemistry in retinal whole-mounts of treated and non-treated PTP-Meg2 deficient and WT control littermates (n = 3-4/group). In order to quantify Brn3a+ RGCs and Iba1+ microglia, cells/mm2 were counted in the peripheral and central part of the retina. Statistical analysis was performed using one-way ANOVA, followed by Tukey`s post-hoc test (Statistica).
PTP-Meg2 HET mice developed significant and progressive IOP elevation upon 9 weeks of age (HET: 15.3±0.3 mmHg, WT: 13.2±0.2 mmHg; p=0.009). Following Latanoprost treatment HET mice underwent a significant IOP reduction (p<0.001). A significant reduction in the number of RGCs was observed in the peripheral retina of non-treated HET animals (3725±151 RGCs/mm2) in comparison to WT mice (5685±168 RGCs/mm2) and Latanoprost-treated HET mice (4770±108 RGCs/mm2; p<0.01). In contrast, no significant differences in the number of RGCs were found in the central retina (p>0.05). Moreover, in comparison to non-treated HET mice, Latanoprost-treated mice showed a significant reduction in the number of peripheral (HET: 805±19 microglia/mm2, HET+LT: 561±66 microglia/mm2; p = 0.03) and central (HET: 840±58 microglia/mm2, HET+LT: 588±31 microglia/mm2, p = 0.02) retinal microglia.
The present study demonstrated that Latanoprost reduces IOP and prevents RGC loss in glaucomatous PTP-Meg HET mice. In addition, reduced microglial reactivity was observed in Latanoprost-treated animals. We speculate that the PTP-Meg2 deficient mouse model may serve as a useful animal model for the preclinical screening of new potentially RGC protective agents.
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