This report describes a potential model of glaucoma 1E, primary open angle (GLC1E); GLC1E exhibits autosomal dominant inheritance. The gene implicated in this disease is OPTN (Optineurin) which encodes a regulatory protein with many roles, including in membrane trafficking and in activation of innate immune response during viral infection.
Multiple constructs of the human Hsap\OPTN gene have been introduced into flies, including wild-type and variants implicated in this disease. A human disease model report has been created for this potential model because variants associated with the disease have been introduced into flies and are available. See the 'Disease Implicated Variants' table, below.
[updated Jan. 2022 by FlyBase; FBrf0222196]
The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to increased levels of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. (Weinreb, et al., 2014; pubmed:24825645)
The fluid in the anterior chamber of the eye is being constantly replenished; intraocular pressure depends on a balance between fluid entering and leaving the eye. Fluid leaves the anterior chamber at the open angle where the cornea and iris meet; when the fluid reaches the angle, it flows through the trabecular meshwork and leaves the eye. In open-angle glaucoma, even though the drainage angle is "open", the fluid passes too slowly through the trabecular meshwork drain. Since the fluid builds up, the pressure inside the eye rises to a level that may damage the optic nerve; in open-angle glaucoma the increase in pressure is very gradual. Eventually, the optic nerve can be damaged from increased pressure and vision loss may result. [https://nei.nih.gov/health/glaucoma/glaucoma_facts]
Angle-closure glaucoma occurs when the iris is very close to the drainage angle of the eye; the iris may block the drainage angle. If the drainage angle gets completely blocked eye pressure rises very quickly, resulting in an acute attack. [https://www.aao.org/eye-health/diseases/what-is-glaucoma]
[GLAUCOMA, PRIMARY OPEN ANGLE; POAG](https://omim.org/entry/137760)
[OPTINEURIN; OPTN](https://omim.org/entry/602432)
Primary open angle glaucoma combines a particular abnormal appearance of the optic disc (optic nerve head) with a slowly progressive loss of visual sensitivity. Changes in the optic disc, either inherited or acquired, contribute to the development of the disorder, which leads to visual loss from increasing nerve fiber layer atrophy (Quigley et al., 1994; pubmed:8185522). [from MIM:137760; 2022.01.03]
This form of adult-onset primary open angle glaucoma (POAG), designated GLC1E, is caused by heterozygous mutation in the OPTN gene. [from MIM:137760; 2022.01.03]
OPTN encodes a regulatory protein that interacts with multiple other proteins. Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, and in exocytosis, through its interaction with myosin VI and Rab8; also interacts with huntingtin and transcription factor IIIA proteins. Plays a neuroprotective role in the eye and optic nerve. Plays a role in the activation of innate immune response during viral infection. [Gene Cards, OPTN; 2022.01.03]
Many to one: 2 human genes to 1 Drosophila gene. The second human gene is IKBKG.