Unraveling the Genetics of Primary Congenital Glaucoma | InformativeBD

Muhammad Umer Khan, Wajeeha Tabassum,  Musbihul Qayyum Zia,  Raima Rehman,  Atif Amin Baig,  Sajjad Ahmed Khan and Rizwan Ahmed Kiani, from the  different institute of Pakistan and Malaysia . wrote a Resview article about, Unraveling the Genetics of Primary Congenital Glaucoma. Entitled, Genetics of primary congenital glaucoma. This research paper published by the International Journal of Biosciences | IJB. an open access scholarly research journal on Biosciences. under the affiliation of the International Network For Natural Sciences| INNSpub. an open access multidisciplinary research journal publisher.

Abstract

Primary Congenital Glaucoma (PCG) is a major risk factor for vision loss in children, which is manifested from birth to three years of age. In PCG the ocular developmental defects of the trabecular meshwork (TM) and front chamber position of eye lead to the blockage of aqueous loss and consequently an increased intraocular pressure (IOP). This results in photophobia, corneal clouding, optic nerve damage, and ultimately permanent loss of vision occurs. The incidence of PCG varies geographically. In Eastern culture, consanguineous marriages may play a role in a higher rate of PCG. Four loci of GLC3A, GLC3B, GLC3C, and 14q24.2-q24.3 to be linked to this ocular condition have been identified. Currently, mutations in two genes i.e.CYP1B1 at GLC3A locus, which encodes cytochrome P4501B1, and LTBP2 at GLC3D locus, which encodes LTBP2is known to cause PCG.CYP1B1 comprises of 3 exons encoding a 543 amino acid protein. CYPIBI is a gene that belongs to the cytochrome P450 family of enzymes. The cytochrome P450 proteins are monooxygenases that catalyse many reactions involved in the synthesis of cholesterol, steroids, other lipids, and drug metabolism. A lot of mutations have been reported in CYP1B1, which results in the form of PCG.

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Introduction

Worldwide, glaucoma is the 2nd leading cause of blindness if it’s left untreated (Hazin et al. 2009). Glaucoma is a collection of optic neuropathies(Quigley et al. 2006). The mark of glaucoma is the hourglass pattern of optic nerve atrophy combined with preferential loss of the more giant ganglion cells of the retina(Schlamp et al. 2006). Anomalies in the conformation or structure of iridocorneal angle may limit the outflow of aqueous humour and make a rise in IOP, which is a primary cause for developing glaucoma (Lewis et al. 2017).

It is currently considered that a variety of etiological factors, acting individually or in a multifactorial fashion, are capable of triggering pathogenetic cascades leading to these lesions. Almost in all types of glaucoma, the drainage system of the eyes becomes blocked, so the intraocular fluid can’t drain. As fluids accumulate, it makes the pressure inside the eye. High pressure in the eye harms the sensitive part of the optic nerve and affects the vision loss.

The syndrome is classified based on analysis, the structure of the front chamber, and the age of onset. Classification of primary forms of glaucoma is done based onthe structure of front chamber as Primary angle-closure glaucoma(PACG), primary open-angle glaucoma(POAG) Primary congenital glaucoma (PCG), (Firasat 2008). POAG was positioned at GLC1A on chromosome 1. MYOC is present at GLC1A, which encodes myocilin protein. Disease linked changes of myocilin generally arise in the infantile or adult form of POAG by increasing level of Intraocular pressure (IOP). In people of adults with POAG, the existence of myocilin alters from 3%-5% (Kwon et al. 2009). In Western populations, Primary open-angle glaucoma is the most common and possibly other communities (Ali et al. 2009, Olawoye et al. 2013).

In PACG, several genes are involved, like myocilin (Rose et al. 2007) optineurin (Shastry 2013) and tryptophan-aspartic acid (W-D) repeat domain 36 (GLC1G)(Monemi et al. 2005)are linked with the autosomal dominant trait. Only 10% of glaucoma is caused by this type(Mandal et al. 2006).PACG is responsible for the most bilateral glaucoma-induced blindness in Singapore, China, and India (Cyrlin 2014, Suri et al. 2015).

Primary congenital glaucoma(PCG) occurs before 3 years of age without any structural defect of the eye(Abu-Amero et al. 2017). PCG is an autosomal recessive disorder with onset at newborn or early juvenile age.

It is affected by developing deficiencies in the trabecular meshwork, and the front cavity angle results in the blockage of aqueous drainage and leads to raised intraocular pressure (Kaur et al. 2011). A comparison of a normal eye and glaucoma eye has been shown in Fig.1(2019).

The covering of the juvenile eye is flexible; it stretches in response to the elevated intraocular pressure that results in an enlarged globe (Chan et al. 2015). Primary Congenital Glaucoma is bilateral in 70 % of patients (Mcculley 2015).

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