This report describes glaucoma 1A, open angle, early-onset (GLC1A), a specific type of glaucoma; GLC1A exhibits autosomal dominant inheritance. The human gene implicated in this disease, MYOC (myocilin), encodes a secreted glycoprotein that regulates the activation of signaling pathways in adjacent cells. MYOC is expressed in many ocular tissues, including the trabecular meshwork, a specialized eye tissue essential in regulating intraocular pressure. There is no gene orthologous to MYOC in Drosophila.
Multiple different UAS constructs of the human Hsap\MYOC gene have been introduced into flies, including wild-type MYOC and genes carrying mutational lesions implicated in GLC1A. Transgenic flies expressing either wild-type or mutant forms of MYOC in the adult eye develop a fluid discharge phenotype and are less responsive to light. The intermittent fluid discharge through the lenses of the compound eye is considered a proxy for increased intraocular pressure, which cannot be measured directly in the Drosophila eye.
Variant(s) implicated in human disease tested (as transgenic human gene, MYOC): K423E and Q368* variant forms of the human gene have been introduced into flies. Additional variants tested that are postulated to be associated with GLC1A: D380N, R342K.
[updated Jun. 2017 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 1, OPEN ANGLE, A; GLC1A](https://omim.org/entry/137750)
[MYOCILIN; MYOC](https://omim.org/entry/601652)
GLC1A is an uncommon form of open angle glaucoma, usually recognized during childhood or early adulthood. Typically, topical medications are initially effective in controlling intraocular pressure, but surgery is usually required for long-term pressure control.
Glaucoma is a group of eye disorders in which the optic nerves are progressively damaged due to increased pressure within the eyes (intraocular pressure). [Genetics Home Reference, early-onset glaucoma; 2017.05.30] See general description, above.
Juvenile open-angle glaucoma is defined as onset between the ages of 10 and 35 years (https://www.reviewofophthalmology.com/article/how-to-manage-juvenile-openangle-glaucoma).
Glaucoma 1A, open angle, early-onset (GLC1A), is caused by heterozygous mutation in the myocilin (MYOC) gene; autosomal dominant. [from MIM:137750; 2017.05.30]
Histopathologic study of the trabecular meshwork in JOAG patients show an abnormally compact trabecular meshwork with an accumulation of extracellular material in the trabecular spaces (https://www.reviewofophthalmology.com/article/how-to-manage-juvenile-openangle-glaucoma).
MYOC encodes the protein myocilin, a secreted glycoprotein that regulates the activation of signaling pathways in adjacent cells to control processes such as cell adhesion, cell-matrix adhesion, cytoskeleton organization, and cell migration. MYOC is expressed in many ocular tissues, including the trabecular meshwork, a specialized eye tissue essential in regulating intraocular pressure. [Gene Cards, MYOC; 2017.05.30]
No gene orthologous to MYOC has been identified in flies.
