Purchase this article with an account.
G. Tosini, S. Alcantara-Contreras, A. Sengupta, K. Baba; Removal of Melatonin Receptor Type 1 Increases Intraocular Pressure and Retinal Ganglion Cells Death in the Mouse. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1628.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Previous studies have shown that intraocular pressure (IOP) can be modulated by melatonin. We have recently reported that mice lacking melatonin receptors type 1 (MT1-/-) showed a significant reduction in the number retinal ganglion cells (RGCs) at 18 months of age with respect to WT mice (Baba et al., PNAS 106: 15043-8; 2009). Aim of the present study was to investigate IOP regulation in MT1-/- mice and whether removal of the melatonin receptor type 2 (MT2) will produce similar effects.
Melatonin receptors (MT1 or MT2) knock-out mice were backcrossed with melatonin proficient mice in which the rd1 mutation has been removed (C3H/f+/+) to generate C3H/f+/+MT1-/- and C3H/f+/+MT2-/-. IOP was measured over the course of the 24-hours using a TonoLab-Tonometer (Icare Finland Ltd.) The number of RGCs was determined in retinal sections using light microscopy.
MT1-/- mice showed a small (4-6 mmHg) but significant (P< 0.05) increase in the IOP at 12 months of age. The increase in the IOP was only present during the nocturnal hours. The increase in IOP was still present at 18 months of age. Differently from what observed in MT1-/-, MT2-/- mice did not show any reduction in the number of RGCs - at least up to the age of 18 months - with respect to WT. MT2-/- mice did not show any significant increase in the in the IOP.
Our results indicate that two key characteristics of primary open angle glaucoma (i.e., loss of RGCs and elevated IOP during aging) are present in MT1-/-. The increase in IOP preceded the loss of RGCs, thus suggesting that such an increase may be responsible for the death of RGCs. Our data indicate that melatonin acting via MT1 receptors modulates IOP in the mouse. Furthermore, our results indicate that even a small (4-6 mmHg) nocturnal increase in IOP over a long period of time may induce a significant loss in GCs (20-30%) over the lifespan of the mouse.
This PDF is available to Subscribers Only