Myocilin & Its Role in Pathogenesis of Juvenile Open Angle Glaucoma

Tathagata Roy, Bachelor’s in  Optometry

Intern Optometrist, Dr. Shroff’s Charity Eye Hospital, New Delhi, India

Compared to adult onset primary open-angle glaucoma (POAG), the Juvenile open angle glaucoma (JOAG) is an autosomal dominant inheritance. Patients complain initially with severe unilateral headache out of proportion to the typical symptoms of chronic ocular hypertension.

Most individuals with JOAG are diagnosed when asymptomatic. It is revealed through genetic linkage analysis of JOAG families that the mutant gene (Myocilin gene – MYOC) is found at the GLC1A locus.⁽¹⁾ This protein is termed as  Myocilin (previously named as trabecular meshwork include- glucocorticoid response protein or TIGR) because of its association of homologous regions with myosin, found in various ocular and non-ocular tissues such as trabecular meshwork, cornea, ciliary nerves, optic nerve, retina and the heart, stomach, bone marrow etc. In the Olfactomedin domain most of the mutations in MYOC associated with glaucoma are occurring. This is one of the major domains of myocilin protein. It is found near the C terminal and consists of 504 amino acids and myosin domain, found near N terminal. ^(2-3)

During stress, greater amounts of MYOC are produced in the eye. There is a possibility of involvement in creating resistance to aqueous outflow through binding to the cell membrane of trabecular meshwork.

If patients with JOAG are symptomatic, then complaints are – blurred vision, ocular pain (due to elevated IOP), or decreased visual acuity at later stages. ^{(4, 5)} Aetiologies like infectious, traumatic, and vascular causes, Horner’s syndrome and cranial nerve palsies would not be found in JOAG. Detailed family history of glaucoma as well as other history that may provide a hint of secondary glaucoma has to be taken from patients. Evaluation of patients presenting with JOAG should include comprehensive ophthalmic assessments such as intraocular pressure (IOP) estimation, Central corneal thickness (CCT) measurement, Anterior chamber angle (ACA) evaluation using gonioscopy technique, optic disc evaluation, and perimetry. An elevation in IOP and open ACA with high iris insertion and prominent iris process can be anticipated. ⁽⁶⁾

Male gender, myopia and family glaucoma history are the main risk factors for JOAG. Rapidly progressive with more severely elevated and fluctuating IOPs ranges 40 to 50 mmHg including axial myopia, mostly diagnosed in between 5 years to less than 35 years, which separate JOAG from POAG. ^(4,5) Monitoring of periodic assessment of IOPs, optic disc and visual fields. Initially topical treatment including beta – blockers, carbonic anhydrase inhibitors and then surgical treatment such as goniotomy, trabeculectomy, Gonioscopy – assisted transluminal trabeculotomy (GATT) and Glaucoma drainage Implants (GDIs) are available to control IOP.

It is important to educate the patients and parents about the nature of the disease and its symptoms as they are at an increased risk of developing visual impairment and blindness. It is possible to increase the chance of preserving vision and preventing permanent visual field loss based on early diagnosis and treatment.

Reference:

1. Alward  WLMFingert  JHCoote  MA Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLCIA).  N Engl J Med. 1998
2. Polansky  JR HTM cell culture model for steroid effects on IOP: overview. Lütjen-Drecoll  Eed Basic Aspects of Glaucoma Research III. Stuttgart, Germany Schattauer1993
3. Polansky  JRFauss  DJChen  P  et al.  Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product.  Ophthalmologica. 1997
4. Hewitt AW, Bennett SL, Fingert JH, et al. The optic nerve head in myocilin glaucoma. Invest Ophthalmol Vis Sci. 2007
5. Ghasia FF, El-Dairi M, Freedman SF, Rajani A, Asrani S. Reproducibility of spectral-domain optical coherence tomography measurements in adult and pediatric glaucoma. J Glaucoma. 2015
6. Kwun Y, Lee EJ, Han JC, Kee C. Clinical Characteristics of Juvenile-onset Open Angle Glaucoma. Korean J Ophthalmol. 2016

IMAGE COURTESY: collected from institutions’ patient record.