**7. Inherited glaucoma in animals**

**Gene Chromosomal**

60 Glaucoma - Basic and Clinical Aspects

ANP MTHFR GSTM1 IL-1beta NCK2 OPA1 PARL EDNRA CDKN1A HSPA1A

be found in ref. # 18.

tions.

**location**

1p36.2 1p36.3 1p13.3 2q14 2q12 3q28-q29 3q27 4q31.2 6p21.2 6p21.3

**Gene Chromosomal**

TNF NOS-3 PON1 TLR4 IGF2 CDH1 TP53 APOE NTF4 AGTR2

ANP = Atrial natriuretic peptide; MTHFR = methylenetetrahydrofolate reductase; IL-1beta = interleukin 1-beta; NCK = adapter protein 2; OPA1 = optic atrophy-1; PARL = presenilin associated rhomboid-like; EDNRA = endothelin receptor type A; CDKN1A = cyclin dependent kinase inhibitor 1A; HSPA1A = heat-shock 70 kD protein 1A; TNF = Tumor necrosis factor; NOS-3 = nitric oxide synthetase –3; PON1 = paraoxonase –1; TLR4 = toll-like receptor 4; IGF2 = insulin-like growth factor 2;CDH-1 = E-cadherin; TP53 = tumor protein p53; APOE = apolipoprotein E; NTF-4 = neurotrophin 4; AGTR2 = angiotensin II receptor type 2; GSTM1 = glutathione S-transferase mu 1; Asterisk (\*) = detailed references can

PACG also involves progressive and irreversible degeneration of the optic nerve with grad‐ ual visual field loss. It is estimated that in Saudi Arabia 40% of glaucoma patients belong to PACG. Although hereditary component for PACG exists, causative genes have not been identified except occasional differences in the frequency of polymorphisms in some genes. For instance, variations in Best disease (BEST1), hepatocyte growth factor (HGF), matrix metalloproteinase - 9 (MMP-9) and methylenetetrahydrofolate reductase (MTHFR) genes have been reported [28]. However, some of these results were not extended to other popula‐

In children, PCG is an important cause of visual loss and diagnosed during the neonatal peri‐ od. It is a heterogeneous group of disorder and is characterized by an elevated IOP due to an abnormal development of the aqueous outflow system. The majority of PCG cases are spora‐ dic but there are some familial cases. The familial condition is inherited as an autosomal reces‐ sive trait with variable expression and penetrance. Recently three PCG loci (2p21, 1p36 and 14q24.3-q31.3) corresponding to GLC3A, GLC3B and GLC 3C genes respectively, have been

**Table 1.** A partial list of genes that are reported to be associated with POAG and NTG \*

**5. Primary angle-closure glaucoma (PACG)**

**6. Primary congenital glaucoma (PCG)**

**location**

6p21.3 7q36 7q21.3 9q32-q33 11p15.5 16q21.1 17p13.1 19q13.2 19q13.3 Xq22-q23

> Inherited glaucoma also occurs in several breeds of dogs including beagles. Primary glauco‐ ma in beagles is inherited as an autosomal recessive trait and appears when the animals are 9 to 18 months old. The pathogenesis, clinical signs and pharmacological responses of glau‐ coma in beagles have been investigated and reported previously [41-43]. Glaucoma in bea‐ gles however, does not involve mutations in MYOC and CYP1B1 genes [44-45]. Similarly, mutations in MYOC gene are unlikely to play a role in the pathogenesis of PCAG in Shiba Inu dogs [46]. Recently, a candidate gene for the beagle model has been isolated [47] and the mutant protein is suggested to be altering the processing of the extracellular matrix that may affect the aqueous humor outflow thereby contributing to the elevated IOP. However, the mechanism underlying RGCs death is not well understood. Interestingly, it was reported that impaired neurotrophin signaling or compromised trophic support as well as p53 medi‐ ated apoptosis may not be the underlying mechanism of RGCs death in a beagle model of glaucoma [48]. Recently, there has been some success in stem cell therapy in animal models [49]. Transplantation of induced pluripotent stem (iPS) cells restored retinal structure and function in degenerative animals. Therefore, these animal models are very useful in further understanding of the pathogenesis as well as drug development in glaucoma.
