Identifying and Studying the Molecules Sensing the Pressure in the Eye
Identify potential candidate molecules, called the Piezo channels, sensing elevated intra-ocular pressure (eIOP) in the retina and modify their activity in laboratory models of glaucoma.
Aim 1: Confirm the presence of Piezo channels in the glaucomatous retina. Identification of the type of cells synthesizing Piezo channels in laboratory models of glaucoma and patient eyes. Aim 2: Modulating the activity of the Piezo channels in the retina of laboratory models of glaucoma using specific drugs. Assessing the effect of Piezo channels modulation on retinal cell death and loss of vision. Aim 3: Confirming that Piezo channels mediate the effect of eIOP in the retina. Assessing the effect of the absence of Piezo genes in the retina of laboratory models of glaucoma.
Uniqueness: - Identification of the molecular sensors mediating the effect of eIOP on retinal cell death and loss of vision in laboratory models and human eyes Innovation: - The use existing pharmacological and genetic approaches to confirm the role of the molecular sensors in glaucoma will speed up the process of validation. - Pharmacological approaches may lead to rapid identification and use of existing drugs, specifically modulating the Piezo channels, to reduce eIOP and block retinal cell death.Biological: Our study may advance the general knowledge of the molecular mechanisms sensing IOP in the eye. Clinical: Clinical trials using existing modulators of Piezo channel activity can be performed. Assessing safety and efficacy of these Piezo channels modulators on retinal cell death and loss of vision in patients with glaucoma.