Non-visual opsins and iris contraction in relation to glaucoma

Glaucoma is a neurodegenerative eye condition and a leading cause of visual impairment and blindness worldwide. Perturbation of the intraocular pressure (IOP) might damage the retinal ganglion cells and their axons, which form the optic nerve, and increase the risk of open-angle glaucoma. Today, reduction of IOP is the main therapeutic mechanism for slowing down the disease progression in patients. Interestingly IOP has long been shown to have a circadian rhythm that is conserved in several species including humans. The rhythmicity of the IOP is normally entrained to the 24h light/dark cycle, with high levels in the night, suggesting that light might play a role for IOP homeostasis.

We are investigating molecular functions of the G-coupled receptors Opsin3 and Opsin4 in the iris-ciliary body complex in relation to IOP homeostasis by modulating Opsin function, either genetically or chemically, followed by analyses of potential targets related to IOP pressure. 

The aim of this study is to decipher the role of Opsin3 and Opsin4 in circadian homeostasis of IOP, and their potential use in open angle glaucoma therapy by finding new candidates for causative and potential cure. Our results show that Opsin3 and Opsin4 are expressed in the ciliary body and the iris already during embryonic development, and that they play distinct roles for the contraction/relaxation of the iris. Our data also provide evidence that the regulation of IOP is intrinsic and independent from retino-thalamic connection, which is in agreement to previous suggestions.